Bhaskar GangulyPh.D. , M.V.Sc., B.V.Sc. & A.H.

TRANSLATIONAL CONTROL&

POST-TRANSLATIONAL MODIFICATIONS

TRANSLATIONAL CONTROL

PROKARYOTES• Structures formed by regions of the mRNA obscure

ribosome binding sites, thus reducing translation of some cistrons relative to others.

• Formation of stems and loops inhibit exonucleases and give certain regions of the polycistronic mRNA a greater half-life.

• Short antisense RNA molecules form duplexes near the ribosome binding site of certain mRNAs.

• Region of an mRNA has a tertiary structure that resembles the binding site for a ribosomal protein encoded by the mRNA. If there is insufficient rRNA available for the translation product to bind to, it will bind to its own mRNA and prevent further translation.

EUKARYOTESTwo common strategies:• Varying the level of transcription of the gene• RNA processing

• Presence of multiple copies of 5-AUUUA-3, usually in the 3-noncoding region, marks the mRNA for rapid degradation.

• Masked mRNA: proteins bind directly to the mRNA and preventing translation; mRNA can be translated when the protein dissociates.

• Non-coding sequences can cause mRNA to be located in a specific part of the cytoplasm and, when translated, can give rise to a gradient of protein concentration across the cell.

Eukaryotes…

• micro RNAs bind to mRNAs to which they are complementary, and either cause degradation or translational repression of the mRNA

• eIF4E inhibitory proteins prevents cap-dependent initiation of translation

• small molecules, e.g. thiamine, can bind to the Shine–Dalgarno sequence of prokaryotic mRNAs and prevent ribosome binding

POLYPROTEINS• Bacteriophage and viral transcripts and many mRNAs for

hormones in eukaryotes (e.g. pro-opiomelanocortin) are translated to give a single polypeptide chain that is cleaved subsequently by specific proteases to produce multiple mature proteins from one translation product.

PROTEIN MODIFICATIONThe modifications include acetylation, hydroxylation, phosphorylation, methylation, glycosylation and even the addition of nucleotides. Hydroxylation of Pro is common in collagen, and some of the histone proteins are often acetylated.

PROTEIN DEGRADATION• The N-terminal residue plays a critical role in inherent

stability.• Eight N-terminal amino acids (Ala, Cys, Gly, Met, Pro, Ser,

Thr, Val) correlate with stability (t1/2 > 20 hours), eight (Arg, His, Ile, Leu, Lys, Phe, Trp, Tyr) with short t1/2 (2–30 min) and four (Asn, Asp, Gln, Glu) are destabilizing following chemical modification.

• Covalent linkage of molecules of the small, highly conserved protein, ubiquitin, via its C-terminal Gly, to lysine residues in the protein.

• Ubiquitinylated protein is digested by a 26S protease complex (proteasome) in a reaction that requires ATP.

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