Post-translational modification (PTM) refers to the covalent and generally enzymatic modification of proteins following protein biosynthesis. Proteins are synthesized by ribosomes translating mRNA into polypeptide chains, which may then undergo PTM to form the mature protein product. PTMs are important components in cell signaling, as for example when prohormones are converted to hormones.

1. NAME: SUVAGIYA DHRUVI
K.
CLASS: MSC. SEM 3
MICROBIOLOGY
TOPIC: REGULATION OF
GENE EXPRESSION IN
EUKARIYOTIC ORGANISMS

3. WHAT IS GENE EXPRESSION??
 Gene expression is the process by which the information encoded in
a gene is used to direct the assembly of a protein molecule. The cell reads
the sequence of the gene in groups of three bases.

4.  Gene expression is the process by which the instructions in our DNA are
converted into a functional product, such as a protein. When the information
stored in our DNAis converted into instructions for making proteins? or
other molecules, it is called gene expression
 Eukaryotic gene expression is the process of the production of gene
products based on the information in the eukaryotic genes. It also occurs
through transcription and translation. Here, since eukaryotic DNA occurs
inside the nucleus, the transcription also occurs inside the nucleus. Three
RNA polymerases are responsible for the transcription of different types of
RNAs: RNA polymerase 1, which synthesizes rRNA, RNA polymerase 2,
which synthesizes mRNA, and RNA polymerase 3, which synthesizes
tRNA. Moreover, each eukaryotic gene is under the control of an individual
promoter. Hence, transcription produces a monocistronic mRNA.
 On the other hand, the primary transcript of mRNA undergoes post-
transcriptional modifications including the addition of a 5’ cap and a 3’ poly
A tail. In addition, the introns that interrupt the protein coding region of the
eukaryotic mRNA are spliced out in a process called RNA splicing. The
ultimate mRNA molecule is the mature mRNA which leaves the nucleus to
the cytoplasm and it is ready for the translation. 80S Ribosomes are
responsible for the translation of the eukaryotic mRNA.

6. REGULATIONS OF GENE EXPRESSION IN EUKAROTES
 Gene expression in eukaryotes regulates at many steps…..
 transcription
 Rna processing
 M-rna transport
 M rna translation
 M rna degradation
 Protein degradation

7. TRANSCRIPTIONAL REGULATION
 In molecular biology and genetics, transcriptional regulation is the means by
which a cell regulates the conversion of DNA to RNA (transcription),
thereby orchestrating gene activity.
 A single gene can be regulated in a range of ways, from altering the number
of copies of RNA that are transcribed, to the temporal control of when the
gene is transcribed.
 This control allows the cell or organism to respond to a variety of intra- and
extracellular signals and thus mount a response.
 Some examples of this include producing the mRNA that encode enzymes
to adapt to a change in a food source, producing the gene products involved
in cell cycle specific activities, and producing the gene products responsible
for cellular differentiation In multicellular eukaryotes, as studied
in evolutionary developmental biology.

9. RNA SPLICING MECHANISMS
 RNA splicing, in molecular biology, is a form of RNA processing in which a
newly made precursor messenger RNA (pre-mRNA) transcript is
transformed into a mature messenger RNA (mRNA). During
splicing, introns (non-coding regions) are removed and exons (coding
regions) are joined together.
 For nuclear-encoded genes, splicing takes place within the nucleus either
during or immediately after transcription. For those eukaryotic genes that
contain introns, splicing is usually required in order to create an mRNA
molecule that can be translated into protein. For many eukaryotic introns,
splicing is carried out in a series of reactions which are catalyzed by
the spliceosome, a complex of small nuclear ribonucleoproteins
(snRNPs). Self-splicing introns, or ribozymes capable of catalyzing their
own excision from their parent RNA molecule, also exist.

11. TRANSLATIONAL CONTROL
 Translational regulation refers to the control of the
levels of protein synthesized from its mRNA.
 This regulation is vastly important to the cellular response to stressors,
growth cues, and differentiation.
 In comparison to transcriptional regulation, it results in much more
immediate cellular adjustment through direct regulation of protein
concentration.
 The corresponding mechanisms are primarily targeted on the control
of ribosome recruitment on the initiation codon, but can also involve
modulation of peptide elongation, termination of protein synthesis,
or ribosome biogenesis.
 While these general concepts are widely conserved.

13. POST TRANSLATION MODIFICATONS
 Post-translational modification (PTM) refers to the covalent and
generally enzymatic modification of proteins following protein
biosynthesis. Proteins are synthesized by ribosomes translating mRNA into
polypeptide chains, which may then undergo PTM to form the mature
protein product. PTMs are important components in cell signaling, as for
example when prohormones are converted to hormones.
 Post-translational modifications can occur on the amino acid side chains or
at the protein's C- or N- termini.[1] They can extend the chemical repertoire
of the 20 standard amino acids by modifying an existing functional group or
introducing a new one such as phosphate. Phosphorylation is a very
common mechanism for regulating the activity of enzymes and is the most
common post-translational modification.[2] Many eukaryotic and
prokaryotic proteins also have carbohydrate molecules attached to them in a
process called glycosylation, which can promote protein folding and
improve stability as well as serving regulatory functions. Attachment
of lipid molecules, known as lipidation, often targets a protein or part of a
protein attached to the cell membrane.

14.  Some types of post-translational modification are consequences of oxidative
stress. Carbonylation is one example that targets the modified protein for
degradation and can result in the formation of protein
aggregates.[4][5] Specific amino acid modifications can be used
as biomarkers indicating oxidative damage.[6]
 Sites that often undergo post-translational modification are those that have a
functional group that can serve as a nucleophile in the reaction:
the hydroxyl groups of serine, threonine, and tyrosine; the amine forms
of lysine, arginine, and histidine; the thiolate anion of cysteine;
the carboxylates of aspartate and glutamate; and the N- and C-termini. In
addition, although the amide of asparagine is a weak nucleophile, it can
serve as an attachment point for glycans. Rarer modifications can occur at
oxidized methionines and at some methylenes in side chains.[7]
 Post-translational modification of proteins can be experimentally detected
by a variety of techniques, including mass spectrometry, Eastern blotting,
and Western blotting. Additional methods are provided in the external links
sections.

15. It can be done by….
 Addition by an enzyme in vivo.
 Hydrophobic groups for membrane localization.
 glypiation, glycosylphosphatidylinositol (GPI) anchor formation via an
amide bond to C-terminal tail
 lipoylation (a type of acylation), attachment of a lipoate (C8) functional
group
 flavin moiety (FMN or FAD) may be covalently attached
 phosphopantetheinylation, the addition of a 4'-phosphopantetheinyl moiety
from coenzyme A, as in fatty acid, polyketide, non-ribosomal peptide and
leucine biosynthesis
 acetylation, the addition of an acetyl group, either at the N-terminus [10] of
the protein or at lysine residues.[11] See also histone acetylation.[12][13] The
reverse is called deacetylation.
 alkylation, the addition of an alkyl group, e.g. methyl, ethyl
 methylation the addition of a methyl group, usually
at lysine or arginine residues. The reverse is called demethylation.

16.  glycosylation, the addition of a glycosyl group to
either arginine, asparagine, cysteine, hydroxylysine, serine, threonine, tyrosine,
or tryptophan resulting in a glycoprotein. Distinct from glycation, which is
regarded as a nonenzymatic attachment of sugars.
 phosphorylation, the addition of a phosphate group, usually to serine, threonine,
and tyrosine (O-linked), or histidine (N-linked)
 sulfation, the addition of a sulfate group to a tyrosine.
 glycation, the addition of a sugar molecule to a protein without the controlling
action of an enzyme.
 carbonylation the addition of carbon monoxide to other organic/inorganic
compounds.
 carbamylation: the addition of Isocyanic acid to a protein's N-terminus or the
side-chain of Lys or Cys residues, typically resulting from exposure to urea
solutions.[20]
 oxidation: addition of one or more Oxygen atoms to a susceptible side-chain,
principally of Met, Trp, His or Cys residues. Formation of disulfide bonds
between Cys residues.
 deamidation, the conversion of glutamine to glutamic
acid or asparagine to aspartic acid
 disulfide bridges, the covalent linkage of two cysteine amino acids
 proteolytic cleavage, cleavage of a protein at a peptide bond
 protein splicing, self-catalytic removal of inteins analogous to mRNA processing