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RNA (Ribonucleic acid ) 
RNA is a 
polymer of 
ribonucleotides 
linked together 
by 3’-5’ 
phosphodiester 
linkage 
3
RNA V/S DNA 
Biochemistry For Medics 4
Differences between RNA and DNA 
S.No. RNA DNA 
1) Single stranded mainly except 
when self complementary 
sequences are there it forms a 
double stranded structure (Hair 
pin structure) 
Double stranded (Except for 
certain viral DNA s which are 
single stranded) 
2) Ribose is the main sugar The sugar moiety is deoxy 
ribose 
3) Pyrimidine components differ. 
Thymine is never found(Except 
tRNA) 
Thymine is always there but 
uracil is never found 
4) Being single stranded structure- 
It does not follow Chargaff’s rule 
It does follow Chargaff's rule. 
The total purine content in a 
double stranded DNA is always 
equal to pyrimidine content. 
Biochemistry For Medics 5
Differences between RNA and DNA 
S.No. RNA DNA 
5) RNA can be easily destroyed by 
alkalies to cyclic diesters of 
mono nucleotides. 
DNA resists alkali action due to 
the absence of OH group at 2’ 
position 
6) RNA is a relatively a labile 
molecule, undergoes easy and 
spontaneous degradation 
DNA is a stable molecule. The 
spontaneous degradation is 
very 2 slow. The genetic 
information can be stored for 
years together without any 
change. 
7) Mainly cytoplasmic, but also 
present in nucleus (primary 
transcript and small nuclear 
RNA) 
Mainly found in nucleus, extra 
nuclear DNA is found in 
mitochondria, and plasmids 
etc 
8) The base content varies from 
100- 5000. The size is variable. 
Millions of base pairs are there 
depending upon the organism 
Biochemistry For Medics 6
Differences between RNA and DNA 
S.No. RNA DNA 
9) There are various types of RNA – 
mRNA, r RNA, t RNA, Sn RNA, Si 
RNA, mi RNA and hn RNA. These 
RNAs perform different and 
specific functions. 
DNA is always of one type and 
performs the function of 
storage and transfer of genetic 
information. 
10) No variable physiological forms 
of RNA are found. The different 
types of RNA do not change 
their forms 
There are variable forms of 
DNA (A to E and Z) 
11) RNA is synthesized from DNA, it 
can not form DNA(except by the 
action of reverse transcriptase). 
It can not duplicate (except in 
certain viruses where it is a 
genomic material ) 
DNA can form DNA by 
replication, it can also form 
RNA by transcription. 
12) Many copies of RNA are present 
per cell 
Single copy of DNA is present 
per cell. 
Biochemistry For Medics 7
Types of RNA 
In all prokaryotic and eukaryotic organisms, 
three main classes of RNA molecules exist- 
1) Messenger RNA(m RNA) 
2) Transfer RNA (t RNA) 
3) Ribosomal RNA (r RNA) 
The other are – 
o small nuclear RNA (SnRNA), 
o micro RNA(mi RNA) and 
o small interfering RNA(Si RNA) and 
o heterogeneous nuclear RNA (hnRNA). 
Biochemistry For Medics 8
Messenger RNA (m-RNA) 
Comprises only 5% of the RNA in the cell 
Most heterogeneous in size and base sequence 
All members of the class function as 
messengers carrying the information in a gene to 
the protein synthesizing machinery 
Biochemistry For Medics 9
Structural Characteristics of 
m-RNA 
The 5’ terminal end is capped by 7- 
methyl guanosine triphosphate cap. 
The cap is involved in the 
recognition of mRNA by the 
translating machinery 
It stabilizes m RNA by protecting it 
from 5’ exonuclease 
Biochemistry For Medics 10
Structural Characteristics of 
m-RNA(contd.) 
 The 3’end of most m-RNAs have a polymer of 
Adenylate residues( 20-250) 
 The tail prevents the attack by 3’ exonucleases 
Histones and interferons do not contain poly A 
tails 
 On both 5’ and 3’ end there are non coding 
sequences which are not translated (NCS) 
The intervening region between non coding 
sequences present between 5’ and 3’ end is 
called coding region. This region encodes for the 
synthesis of a protein. 
Biochemistry For Medics 11
Structural Characteristics of 
m-RNA 
5’ cap and 3’ tail impart stability to m RNA by protecting from 
specific exo nucleases. 
Biochemistry For Medics 12
Structural Characteristics of 
m-RNA(Contd.) 
The m- RNA molecules are formed with the help of 
DNA template during the process of transcription. 
The sequence of nucleotides in m RNA is 
complementary to the sequence of nucleotides on 
template DNA. 
The sequence carried on m -RNA is read in the form 
of codons. 
A codon is made up of 3 nucleotides 
The m-RNA is formed after processing of 
heterogeneous nuclear RNA 
Biochemistry For Medics 13
Heterogeneous nuclear RNA 
(hnRNA) 
 In mammalian nuclei , hnRNA is the 
immediate product of gene transcription 
 The nuclear product is heterogeneous in size 
(Variable) and is very large. 
Molecular weight may be more than 107, while 
the molecular weight of m RNA is less than 2x 106 
 75 % of hnRNA is degraded in the nucleus, 
only 25% is processed to mature 
m RNA 
Biochemistry For Medics 14
Heterogeneous nuclear RNA 
(hnRNA) 
Mature m –RNA is formed from primary transcript by 
capping, tailing, splicing and base modification. 
Biochemistry For Medics 15
Transfer RNA (t- RNA) 
Transfer RNA are the smallest of three major species of 
RNA molecules 
They have 74-95 nucleotide residues 
 They are synthesized by the nuclear processing of a 
precursor molecule 
They transfer the amino acids from cytoplasm to the 
protein synthesizing machinery, hence the name t RNA. 
They are easily soluble , hence called “Soluble RNA or s 
RNA 
They are also called Adapter molecules, since they act as 
adapters for the translation of the sequence of nucleotides 
of the m RNA in to specific amino acids 
There are at least 20 species of t RNA one corresponding 
to each of the 20 amino acids required for protein 
synthesis. 
Biochemistry For Medics 16
Structural characteristics of t- RNA 
1) Primary structure- The nucleotide 
sequence of all the t RNA molecules allows 
extensive intrastand complimentarity that 
generates a secondary structure. 
2) Secondary structure- Each single t- RNA 
shows extensive internal base pairing and 
acquires a clover leaf like structure. The 
structure is stabilized by hydrogen bonding 
between the bases and is a consistent 
feature. 
Biochemistry For Medics 17
Structural characteristics of t- 
RNA 
Secondary structure (Clover leaf structure) 
All t-RNA contain 5 main arms or loops 
which are as follows-a) 
Acceptor arm 
b) Anticodon arm 
c) D HU arm 
d) TΨ C arm 
e) Extra arm 
Biochemistry For Medics 18
Secondary structure of t- RNA 
a) Acceptor arm 
 The acceptor arm is at 3’ end 
 It has 7 base pairs 
 The end sequence is unpaired Cytosine, 
Cytosine-Adenine at the 3’ end 
 The 3’ OH group terminal of Adenine binds with 
carboxyl group of amino acids 
 The t RNA bound with amino acid is called 
Amino acyl t RNA 
 CCA attachment is done post transcriptionally 
Biochemistry For Medics 19
Secondary structure of t- RNA 
The carboxyl group of amino acid is attached to 3’OH group of Adenine 
nucleotide of the acceptor arm. The anticodon arm base pairs with the codon 
present on the m- RNA 
Biochemistry For Medics 20
Secondary structure of t- 
RNA(contd.) 
b) Anticodon arm 
 Lies at the opposite end of acceptor arm 
5 base pairs long 
Recognizes the triplet codon present in the m 
RNA 
Base sequence of anticodon arm is 
complementary to the base sequence of m RNA 
codon. 
 Due to complimentarity it can bind specifically 
with m RNA by hydrogen bonds. 
Biochemistry For Medics 21
Secondary structure of t- 
RNA(contd.) 
c) DHU arm 
 It has 3-4 base pairs 
Serves as the recognition site for the enzyme (amino 
acyl t RNA synthetase) that adds the amino acid to the 
acceptor arm. 
d) TΨC arm 
This arm is opposite to DHU arm 
Since it contains pseudo uridine that is why it is so 
named 
 It is involved in the binding of t RNA to the ribosomes 
Biochemistry For Medics 22
Secondary structure of t- 
RNA(contd.) 
e) Extra arm or Variable arm 
 About 75 % of t RNA molecules possess 
a short extra arm 
If about 3-5 base pairs are present the 
t-RNA is said to be belonging to class 1. 
Majority t -RNA belong to class 1. 
 The t –RNA belonging to class 2 have 
long extra arm, 13-21 base pairs in length. 
Biochemistry For Medics 23
Tertiary structure of t- RNA 
 The L shaped tertiary 
structure is formed by 
further folding of the clover 
leaf due to hydrogen bonds 
between T and D arms. 
 The base paired double 
helical stems get arranged in 
to two double helical 
columns, continuous and 
perpendicular to one 
another. 
Biochemistry For Medics 24
Ribosomal RNA (rRNA) 
The mammalian ribosome contains two major 
nucleoprotein subunits—a larger one with a molecular 
weight of 2.8 x 106 (60S) and a smaller subunit with a 
molecular weight of 1.4 x 106 (40S). 
The 60S subunit contains a 5S ribosomal RNA (rRNA), a 
5.8S rRNA, and a 28S rRNA; there are also probably more 
than 50 specific polypeptides. 
The 40S subunit is smaller and contains a single 18S 
rRNA and approximately 30 distinct polypeptide chains. 
All of the ribosomal RNA molecules except the 5S rRNA 
are processed from a single 45S precursor RNA molecule 
in the nucleolus . 
5S rRNA is independently transcribed. 
Biochemistry For Medics 25
Ribosomal RNA (rRNA) 
Biochemistry For Medics 26
Ribosomal RNA (rRNA) 
The functions of the ribosomal RNA 
molecules in the ribosomal particle are not 
fully understood, but they are necessary for 
ribosomal assembly and seem to play key 
roles in the binding of mRNA to ribosomes 
and its translation 
Recent studies suggest that an rRNA 
component performs the peptidyl transferase 
activity and thus is an enzyme (a ribozyme). 
Biochemistry For Medics 27
Small RNA 
Most of these molecules are 
complexed with proteins to form 
ribonucleoproteins and are distributed in 
the nucleus, in the cytoplasm, or in both. 
They range in size from 20 to 300 
nucleotides and are present in 100,000– 
1,000,000 copies per cell. 
Biochemistry For Medics 28
Small Nuclear RNAs (snRNAs) 
snRNAs, a subset of the small RNAs, are 
significantly involved in mRNA processing and 
gene regulation 
Of the several snRNAs, U1, U2, U4, U5, and 
U6 are involved in intron removal and the 
processing of hnRNA into mRNA 
The U7 snRNA is involved in production of 
the correct 3' ends of histone mRNA—which 
lacks a poly(A) tail. 
Biochemistry For Medics 29
Small Nuclear RNAs (snRNAs). 
Sn RNA s are involved in the process of splicing (intron removal) of primary 
transcript to form mature m RNA. The Sn RNA s form complexes with proteins 
to form Ribonucleoprotein particles called snRNPs 
Biochemistry For Medics 30
Micro RNAs, miRNAs, and Small 
Interfering RNAs, siRNAs 
These two classes of RNAs represent a 
subset of small RNAs; both play important 
roles in gene regulation. 
miRNAs and siRNAs cause inhibition of 
gene expression by decreasing specific 
protein production albeit apparently via 
distinct mechanisms 
Biochemistry For Medics 31
Micro RNAs (miRNAs) 
miRNAs are typically 21–25 nucleotides in 
length and are generated by nucleolytic 
processing of the products of distinct 
genes/transcription units 
The small processed mature miRNAs 
typically hybridize, via the formation of 
imperfect RNA-RNA duplexes within the 3'- 
untranslated regions of specific target 
mRNAs, leading via unknown mechanisms to 
translation arrest. 
Biochemistry For Medics 32
Micro RNAs (miRNAs) 
microRNAs, short non-coding RNAs present in all living organisms, have 
been shown to regulate the expression of at least half of all human 
genes. These single-stranded RNAs exert their regulatory action by 
binding messenger RNAs and preventing their translation into 
proteins. 
Biochemistry For Medics 33
Small Interfering RNAs (siRNAs) 
 siRNAs are derived by the specific nucleolytic cleavage 
of larger, double-stranded RNAs to again form small 21– 
25 nucleotide-long products. 
These short siRNAs usually form perfect RNA-RNA 
hybrids with their distinct targets potentially anywhere 
within the length of the mRNA where the complementary 
sequence exists. 
 Formation of such RNA-RNA duplexes between siRNA 
and mRNA results in reduced specific protein production 
because the siRNA-mRNA complexes are degraded by 
dedicated nucleolytic machinery; 
 some or all of this mRNA degradation occurs in specific 
organelles termed P bodies. 
Biochemistry For Medics 34
Small Interfering RNAs (siRNAs) 
Small interfering RNA (siRNA) are 20-25 nucleotide-long double-stranded RNA 
molecules that have a variety of roles in the cell. They are involved in the RNA 
interference (RNAi) pathway, where it interferes with the expression of a 
specific gene by hybridizing to its corresponding RNA sequence in the 
target mRNA. This then activates the degrading mRNA. Once the target 
mRNA is degraded, the mRNA caBinocnheomtis tbrye F otr rMaendiscslated into protein. 35
Significance of mi RNAs and si 
RNAs 
Both miRNAs and siRNAs represent 
exciting new potential targets for 
therapeutic drug development in humans. 
In addition, siRNAs are frequently used to 
decrease or "knock-down" specific protein 
levels in experimental procedures in the 
laboratory, an extremely useful and 
powerful alternative to gene-knockout 
technology. 
Biochemistry For Medics 36
Summary 
RNA exists in several different single-stranded 
structures, most of which are directly or indirectly 
involved in protein synthesis or its regulation. 
The linear array of nucleotides in RNA consists of A, G, 
C, and U, and the sugar moiety is ribose. 
The major forms of RNA include messenger RNA 
(mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), 
and small nuclear RNAs (snRNAs; miRNAs). 
 Certain RNA molecules act as catalysts (ribozymes). 
miRNAs and siRNAs represent exciting new potential 
targets for therapeutic drug development in humans. 
Biochemistry For Medics 37

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RNA

  • 1. 1
  • 2. 2
  • 3. RNA (Ribonucleic acid ) RNA is a polymer of ribonucleotides linked together by 3’-5’ phosphodiester linkage 3
  • 4. RNA V/S DNA Biochemistry For Medics 4
  • 5. Differences between RNA and DNA S.No. RNA DNA 1) Single stranded mainly except when self complementary sequences are there it forms a double stranded structure (Hair pin structure) Double stranded (Except for certain viral DNA s which are single stranded) 2) Ribose is the main sugar The sugar moiety is deoxy ribose 3) Pyrimidine components differ. Thymine is never found(Except tRNA) Thymine is always there but uracil is never found 4) Being single stranded structure- It does not follow Chargaff’s rule It does follow Chargaff's rule. The total purine content in a double stranded DNA is always equal to pyrimidine content. Biochemistry For Medics 5
  • 6. Differences between RNA and DNA S.No. RNA DNA 5) RNA can be easily destroyed by alkalies to cyclic diesters of mono nucleotides. DNA resists alkali action due to the absence of OH group at 2’ position 6) RNA is a relatively a labile molecule, undergoes easy and spontaneous degradation DNA is a stable molecule. The spontaneous degradation is very 2 slow. The genetic information can be stored for years together without any change. 7) Mainly cytoplasmic, but also present in nucleus (primary transcript and small nuclear RNA) Mainly found in nucleus, extra nuclear DNA is found in mitochondria, and plasmids etc 8) The base content varies from 100- 5000. The size is variable. Millions of base pairs are there depending upon the organism Biochemistry For Medics 6
  • 7. Differences between RNA and DNA S.No. RNA DNA 9) There are various types of RNA – mRNA, r RNA, t RNA, Sn RNA, Si RNA, mi RNA and hn RNA. These RNAs perform different and specific functions. DNA is always of one type and performs the function of storage and transfer of genetic information. 10) No variable physiological forms of RNA are found. The different types of RNA do not change their forms There are variable forms of DNA (A to E and Z) 11) RNA is synthesized from DNA, it can not form DNA(except by the action of reverse transcriptase). It can not duplicate (except in certain viruses where it is a genomic material ) DNA can form DNA by replication, it can also form RNA by transcription. 12) Many copies of RNA are present per cell Single copy of DNA is present per cell. Biochemistry For Medics 7
  • 8. Types of RNA In all prokaryotic and eukaryotic organisms, three main classes of RNA molecules exist- 1) Messenger RNA(m RNA) 2) Transfer RNA (t RNA) 3) Ribosomal RNA (r RNA) The other are – o small nuclear RNA (SnRNA), o micro RNA(mi RNA) and o small interfering RNA(Si RNA) and o heterogeneous nuclear RNA (hnRNA). Biochemistry For Medics 8
  • 9. Messenger RNA (m-RNA) Comprises only 5% of the RNA in the cell Most heterogeneous in size and base sequence All members of the class function as messengers carrying the information in a gene to the protein synthesizing machinery Biochemistry For Medics 9
  • 10. Structural Characteristics of m-RNA The 5’ terminal end is capped by 7- methyl guanosine triphosphate cap. The cap is involved in the recognition of mRNA by the translating machinery It stabilizes m RNA by protecting it from 5’ exonuclease Biochemistry For Medics 10
  • 11. Structural Characteristics of m-RNA(contd.)  The 3’end of most m-RNAs have a polymer of Adenylate residues( 20-250)  The tail prevents the attack by 3’ exonucleases Histones and interferons do not contain poly A tails  On both 5’ and 3’ end there are non coding sequences which are not translated (NCS) The intervening region between non coding sequences present between 5’ and 3’ end is called coding region. This region encodes for the synthesis of a protein. Biochemistry For Medics 11
  • 12. Structural Characteristics of m-RNA 5’ cap and 3’ tail impart stability to m RNA by protecting from specific exo nucleases. Biochemistry For Medics 12
  • 13. Structural Characteristics of m-RNA(Contd.) The m- RNA molecules are formed with the help of DNA template during the process of transcription. The sequence of nucleotides in m RNA is complementary to the sequence of nucleotides on template DNA. The sequence carried on m -RNA is read in the form of codons. A codon is made up of 3 nucleotides The m-RNA is formed after processing of heterogeneous nuclear RNA Biochemistry For Medics 13
  • 14. Heterogeneous nuclear RNA (hnRNA)  In mammalian nuclei , hnRNA is the immediate product of gene transcription  The nuclear product is heterogeneous in size (Variable) and is very large. Molecular weight may be more than 107, while the molecular weight of m RNA is less than 2x 106  75 % of hnRNA is degraded in the nucleus, only 25% is processed to mature m RNA Biochemistry For Medics 14
  • 15. Heterogeneous nuclear RNA (hnRNA) Mature m –RNA is formed from primary transcript by capping, tailing, splicing and base modification. Biochemistry For Medics 15
  • 16. Transfer RNA (t- RNA) Transfer RNA are the smallest of three major species of RNA molecules They have 74-95 nucleotide residues  They are synthesized by the nuclear processing of a precursor molecule They transfer the amino acids from cytoplasm to the protein synthesizing machinery, hence the name t RNA. They are easily soluble , hence called “Soluble RNA or s RNA They are also called Adapter molecules, since they act as adapters for the translation of the sequence of nucleotides of the m RNA in to specific amino acids There are at least 20 species of t RNA one corresponding to each of the 20 amino acids required for protein synthesis. Biochemistry For Medics 16
  • 17. Structural characteristics of t- RNA 1) Primary structure- The nucleotide sequence of all the t RNA molecules allows extensive intrastand complimentarity that generates a secondary structure. 2) Secondary structure- Each single t- RNA shows extensive internal base pairing and acquires a clover leaf like structure. The structure is stabilized by hydrogen bonding between the bases and is a consistent feature. Biochemistry For Medics 17
  • 18. Structural characteristics of t- RNA Secondary structure (Clover leaf structure) All t-RNA contain 5 main arms or loops which are as follows-a) Acceptor arm b) Anticodon arm c) D HU arm d) TΨ C arm e) Extra arm Biochemistry For Medics 18
  • 19. Secondary structure of t- RNA a) Acceptor arm  The acceptor arm is at 3’ end  It has 7 base pairs  The end sequence is unpaired Cytosine, Cytosine-Adenine at the 3’ end  The 3’ OH group terminal of Adenine binds with carboxyl group of amino acids  The t RNA bound with amino acid is called Amino acyl t RNA  CCA attachment is done post transcriptionally Biochemistry For Medics 19
  • 20. Secondary structure of t- RNA The carboxyl group of amino acid is attached to 3’OH group of Adenine nucleotide of the acceptor arm. The anticodon arm base pairs with the codon present on the m- RNA Biochemistry For Medics 20
  • 21. Secondary structure of t- RNA(contd.) b) Anticodon arm  Lies at the opposite end of acceptor arm 5 base pairs long Recognizes the triplet codon present in the m RNA Base sequence of anticodon arm is complementary to the base sequence of m RNA codon.  Due to complimentarity it can bind specifically with m RNA by hydrogen bonds. Biochemistry For Medics 21
  • 22. Secondary structure of t- RNA(contd.) c) DHU arm  It has 3-4 base pairs Serves as the recognition site for the enzyme (amino acyl t RNA synthetase) that adds the amino acid to the acceptor arm. d) TΨC arm This arm is opposite to DHU arm Since it contains pseudo uridine that is why it is so named  It is involved in the binding of t RNA to the ribosomes Biochemistry For Medics 22
  • 23. Secondary structure of t- RNA(contd.) e) Extra arm or Variable arm  About 75 % of t RNA molecules possess a short extra arm If about 3-5 base pairs are present the t-RNA is said to be belonging to class 1. Majority t -RNA belong to class 1.  The t –RNA belonging to class 2 have long extra arm, 13-21 base pairs in length. Biochemistry For Medics 23
  • 24. Tertiary structure of t- RNA  The L shaped tertiary structure is formed by further folding of the clover leaf due to hydrogen bonds between T and D arms.  The base paired double helical stems get arranged in to two double helical columns, continuous and perpendicular to one another. Biochemistry For Medics 24
  • 25. Ribosomal RNA (rRNA) The mammalian ribosome contains two major nucleoprotein subunits—a larger one with a molecular weight of 2.8 x 106 (60S) and a smaller subunit with a molecular weight of 1.4 x 106 (40S). The 60S subunit contains a 5S ribosomal RNA (rRNA), a 5.8S rRNA, and a 28S rRNA; there are also probably more than 50 specific polypeptides. The 40S subunit is smaller and contains a single 18S rRNA and approximately 30 distinct polypeptide chains. All of the ribosomal RNA molecules except the 5S rRNA are processed from a single 45S precursor RNA molecule in the nucleolus . 5S rRNA is independently transcribed. Biochemistry For Medics 25
  • 26. Ribosomal RNA (rRNA) Biochemistry For Medics 26
  • 27. Ribosomal RNA (rRNA) The functions of the ribosomal RNA molecules in the ribosomal particle are not fully understood, but they are necessary for ribosomal assembly and seem to play key roles in the binding of mRNA to ribosomes and its translation Recent studies suggest that an rRNA component performs the peptidyl transferase activity and thus is an enzyme (a ribozyme). Biochemistry For Medics 27
  • 28. Small RNA Most of these molecules are complexed with proteins to form ribonucleoproteins and are distributed in the nucleus, in the cytoplasm, or in both. They range in size from 20 to 300 nucleotides and are present in 100,000– 1,000,000 copies per cell. Biochemistry For Medics 28
  • 29. Small Nuclear RNAs (snRNAs) snRNAs, a subset of the small RNAs, are significantly involved in mRNA processing and gene regulation Of the several snRNAs, U1, U2, U4, U5, and U6 are involved in intron removal and the processing of hnRNA into mRNA The U7 snRNA is involved in production of the correct 3' ends of histone mRNA—which lacks a poly(A) tail. Biochemistry For Medics 29
  • 30. Small Nuclear RNAs (snRNAs). Sn RNA s are involved in the process of splicing (intron removal) of primary transcript to form mature m RNA. The Sn RNA s form complexes with proteins to form Ribonucleoprotein particles called snRNPs Biochemistry For Medics 30
  • 31. Micro RNAs, miRNAs, and Small Interfering RNAs, siRNAs These two classes of RNAs represent a subset of small RNAs; both play important roles in gene regulation. miRNAs and siRNAs cause inhibition of gene expression by decreasing specific protein production albeit apparently via distinct mechanisms Biochemistry For Medics 31
  • 32. Micro RNAs (miRNAs) miRNAs are typically 21–25 nucleotides in length and are generated by nucleolytic processing of the products of distinct genes/transcription units The small processed mature miRNAs typically hybridize, via the formation of imperfect RNA-RNA duplexes within the 3'- untranslated regions of specific target mRNAs, leading via unknown mechanisms to translation arrest. Biochemistry For Medics 32
  • 33. Micro RNAs (miRNAs) microRNAs, short non-coding RNAs present in all living organisms, have been shown to regulate the expression of at least half of all human genes. These single-stranded RNAs exert their regulatory action by binding messenger RNAs and preventing their translation into proteins. Biochemistry For Medics 33
  • 34. Small Interfering RNAs (siRNAs)  siRNAs are derived by the specific nucleolytic cleavage of larger, double-stranded RNAs to again form small 21– 25 nucleotide-long products. These short siRNAs usually form perfect RNA-RNA hybrids with their distinct targets potentially anywhere within the length of the mRNA where the complementary sequence exists.  Formation of such RNA-RNA duplexes between siRNA and mRNA results in reduced specific protein production because the siRNA-mRNA complexes are degraded by dedicated nucleolytic machinery;  some or all of this mRNA degradation occurs in specific organelles termed P bodies. Biochemistry For Medics 34
  • 35. Small Interfering RNAs (siRNAs) Small interfering RNA (siRNA) are 20-25 nucleotide-long double-stranded RNA molecules that have a variety of roles in the cell. They are involved in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene by hybridizing to its corresponding RNA sequence in the target mRNA. This then activates the degrading mRNA. Once the target mRNA is degraded, the mRNA caBinocnheomtis tbrye F otr rMaendiscslated into protein. 35
  • 36. Significance of mi RNAs and si RNAs Both miRNAs and siRNAs represent exciting new potential targets for therapeutic drug development in humans. In addition, siRNAs are frequently used to decrease or "knock-down" specific protein levels in experimental procedures in the laboratory, an extremely useful and powerful alternative to gene-knockout technology. Biochemistry For Medics 36
  • 37. Summary RNA exists in several different single-stranded structures, most of which are directly or indirectly involved in protein synthesis or its regulation. The linear array of nucleotides in RNA consists of A, G, C, and U, and the sugar moiety is ribose. The major forms of RNA include messenger RNA (mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNAs (snRNAs; miRNAs).  Certain RNA molecules act as catalysts (ribozymes). miRNAs and siRNAs represent exciting new potential targets for therapeutic drug development in humans. Biochemistry For Medics 37