Call Girls Horamavu WhatsApp Number 7001035870 Meeting With Bangalore Escorts
Rna and truncated form in health and diseases
1. RNA and its Truncated form in
Health & Diseases
Dr. Gaurav Kumar
King Georges Medical university
2. RNA (Ribonucleic Acid)
• Polymer of
ribonucleotides
linked by 3’-5’
phosphodiester
linkage
• Ribonucleotide
– a ribose sugar,
nucleic acid
base and
phosphate
group
3. RNA
• Synthesized from DNA by RNA polymerase
• DNA preRNA (hnRNA) mRNA
• Intron – non coding sequences
• Exon – coding sequences
4. Types Of RNA
• Three main classes of RNA molecules-
1. Messenger RNA(m RNA)
2. Transfer RNA (t RNA)
3. Ribosomal RNA (r RNA)
• The other are –
1. small nuclear RNA (SnRNA),
2. micro RNA(mi RNA)
3. small interfering RNA(Si RNA)
4. heterogeneous nuclear RNA (hnRNA).
5. mRNA
• Synthesized in nucleus in eukaryotes as
hnRNA.
• Carries genetic material to the ribosomes
• High molecular weight and short T1/2
6. • 5’ end – capping (to prevent hydrolysis by
exonucleases) – 7methyl guanosine
• 3’ end – poly A tail (stability) - polyadenylation
7. tRNA
• Soluble RNA
• Clover leaf structure
• 4 arms
– Acceptor arm
– Anticodon arm
– D arm
– TΨC arm
10. Mutation can occur in
• Ribosome biogenesis
• Splicing
• Telomerase
• Protein kinase
• RNA binding protein
11. Ribosome biogenesis
• Ribosomes are the cellular factories for
protein synthesis
• Multiple enzymes, transcription factors are
required
12. rRN
ArRNA
Small ribosomal subunit protein
Large ribosomal subunit protein
Ribosome biogenesis protein
Small nucleolar ribonuclear protein
Ribosomal protein
• Treacher collins syndrome
• North American Indian
Childhood cirrhosis
• Schwachman Bodian
Diamond Syndrome
• POAG
• HCA66 modifier of NF1
• Diamond Blackfan Anemia
• 5q deletion syndrome
15. Mutation that causes splicing defect
Cis- acting
mutations
Trans Acting
mutation
Mutation in
spliceosome
Change in
snRNP
receptors
Change in
splicing
factors
Acting from the same molecules
Acting from the
different
molecules
16. Trans-acting
• DNA sequence contains
a gene
• This gene encodes for a
protein
• This protein will be used
in the regulation of
another target gene.
Cis-acting
• Regions of non coding
DNA
• Regulate the
transcription of
neighboring gene
• They are found in the
vicinity of the
regulatory gene
19. Gain of function mutation
• Also called microsatellite expansion disorders
• RNA gain of function is seen in
– Myotonic dystrophy types 1 and 2
– Fragile X associated tremor ataxia syndrome
– Spinocerebellar ataxia
28. RNA as Therapeutic target
• To modify the splicing pattern of a mutant pre
RNA
• To eliminate the defected mRNA
• Include
– Antisense oligonucleotides
– Antisense snRNAs
– RNA interference
– Small molecules
29. Antisense Oligonucleotides
• Antisense oligonucleotides are synthetic
polymers
• The monomers are chemically-modified
deoxynucleotides or ribonucleotides
• There are usually only 15–20 of them, hence
"oligo".
• Their sequence (3′ → 5′) is antisense; that is,
complementary to the sense sequence of a
molecule of mRNA.
30. • Used to redirect splicing of mutant pre-mRNA
• Blocking disease processes by altering the
synthesis of a particular protein.
• Under trial in some disease
– Beta- thalassemia
– CFTR gene in cystic fibrosis
– Lamin A gene in Hutchinson progeria disease
31. snRNAs as Vehicles for Stable
Antisense RNAs
• RNA can be used as a tool to target preRNA by
antisense hybridization
• snRNA acts as a vector
• Antisense RNA- RNA copied from antisense
strand of DNA
• Hybridization can prevent the expression of
desired gene
• In mouse model – treatment of Duchene
muscular dystrophy
32. Small molecules
• Splicing is strongly dependent on serine-
arginine-rich (SR) proteins and hnRNP proteins
• Small molecules that affect their activities or
their relative amounts in the nucleus can
modify splicing.
• Under study for Papillary Thyroid carcinoma
33. Refrences
• Cooper, Thomas et al. “RNA and Disease”. Cell,
volume 136, issue 4, 777-793
• Calado, Rodrigo T., and Neal S. Young. “Telomere
Diseases.” The New England Journal of Medicine
361.24 (2009): 2353–2365. PMC. Web. 2 Dec.
2017.
• Freed, Emily F. et al. “When Ribosomes Go Bad:
Diseases of Ribosome Biogenesis.” Molecular
bioSystems 6.3 (2010): 481–493. PMC. Web. 2
Dec. 2017.
34. 1- Sequence of codons in the telomere is:
a) GGGTTT
b) TTAGGG
c) CCCGGT
d) AAUCCC
35. 2- Thalassemia occurs due to defect in :
a) RNA biogenesis protein
b) Splicing
c) Telomerase defect
d) Kinase dependent protein
36. 3- Nucleoside is:
a) Base + sugar + phosphate
b) Base + sugar
c) Base + phosphate
d) Sugar + phosphate
37. 4- Which of the disease occurs due to gain of
function mutation?
a) Diamond blackfan anemia
b) Myotonic dystrophy
c) Amyotrophic Lateral Sclerosis
d) Retinitis pigmentosa