Question

With diagrams, describe two different mechanisms in which gene expression is controlled at the translational and post-translational levels. You must cite an example for each of these control mechanisms.

Answer 1

Translational regulation of gene expression is an important mechanism of gene expression regulation. In this mechanism, the efficiency of the translational machinery is affected either positively or negatively by regulating any of the rate-limiting factors involved in translation.

Example- Unfolded protein response (UPR) in the endoplasmic reticulum (ER) during stress. Global downregulation of translation occurs during this response.

Step by step mechanism-

1)      Endoplasmic reticulum (ER) stress activates PKR-like ER kinase (PERK) which is a transmembrane protein of ER. In normal condition, the UPR transducers like PERK, associate with BiP to prevent UPR. On accumulation of misfolded proteins in the ER lumen, BiP dissociates to activate UPR transducers.

2)      The PERK protein bears luminal domain coupled across the ER membrane to the cytosolic kinase domain (K).

3)      In response to ER stress, PERK dimerizes and subsequently activates its cytosolic kinase domain.

4)      PERK's kinase recognizes and phosphorylates eukaryotic translation initiation factor 2 subunit alpha (eIF2α), leading to attenuation of global protein translation.

ER Normal - Stress (UPR). Bip CIK ® PERk Cactive) PERK cinactive) (eIF 2.c elF22 (Active) (Inactive) AAAA MRNA (608) cattenuation of global protein translation )

Post-translational regulation of gene expression means the regulation is at the level of protein activity after translation is complete. This is usually done by proteolytic processing, post-translational modifications or sequestration of the protein.

Example- Transcription factor NFAT has an important role during T-cell activation. The activity of the transcription factor NFAT is controlled by post-translational regulation. After translation, it is inactivated by phosphorylation. During phospholipase C (PLC gamma) mediated signal transduction, it is activated by removal of the inhibitory phosphate group by a phosphatase enzyme (calcineurin) and then it migrates into the nucleus to exert its effects.

- Plasma membrane -> SE (PZPR membrane P1P2 PLCY cinactive) PLCY (active) - IP3 DAG calmodulin (inactive) ca²+ 2 ca²* ER ca²t calmoclulin Cactive) calcinenrin cactive) e calcineurin (inactive) NFAT-Ⓡ (inactive) NFAT + nucleus NFAT (active) Transcription