[Cis-regulatory mechanisms and biological effects of translation elongation].

Proteins are biological macromolecules essential for cells to maintain their metabolic activities. Proteins are synthesized during translation elongation, a synergistic process in which ribosomes decode the genetic information transmitted in mRNA, using tRNA. Numerous human diseases, such as neurodegenerative diseases and cancers, are known to be related to abnormal translation elongation. Translation elongation, as one of the two critical steps for the central dogma, used to be the focus of research in molecular biology. However, limitations in methodology had hindered further investigations on the dynamic process of translation elongation and its regulation. Recently, breakthroughs in methodology have revived this research field. Studies in the past decade or so have revealed that, beyond simple decoding of genetic information in mRNA, translation elongation entails sophisticated regulatory mechanisms and multifaceted biological consequences; such insights have provided a novel theoretical framework for understanding the maintenance of protein homeostasis and the development of diseases. In this review, we summarize the most updated methods that can be used to investigate the processes of translation elongation and highlight the mechanisms by which mRNA and protein sequences modulate the local rate of translation elongation. We further enumerate the consequences of dysregulation in translation elongation, from various aspects such as mRNA stability, protein synthesis and degradation, protein subcellular localization, and co-translational protein folding. We anticipate that this review will serve to draw the attention of scholars in various research fields to participate in the study of translation elongation.

PARAQUAT TOLERANCE3 Is an E3 Ligase That Switches off Activated Oxidative Response by Targeting Histone-Modifying PROTEIN METHYLTRANSFERASE4b.

Oxidative stress is unavoidable for aerobic organisms. When abiotic and biotic stresses are encountered, oxidative damage could occur in cells. To avoid this damage, defense mechanisms must be timely and efficiently modulated. While the response to oxidative stress has been extensively studied in plants, little is known about how the activated response is switched off when oxidative stress is diminished. By studying Arabidopsis mutant paraquat tolerance3, we identified the genetic locus PARAQUAT TOLERANCE3 (PQT3) as a major negative regulator of oxidative stress tolerance. PQT3, encoding an E3 ubiquitin ligase, is rapidly down-regulated by oxidative stress. PQT3 has E3 ubiquitin ligase activity in ubiquitination assay. Subsequently, we identified PRMT4b as a PQT3-interacting protein. By histone methylation, PRMT4b upregulates the expression of APX1 and GPX1, encoding two key enzymes against oxidative stress. On the other hand, PRMT4b is recognized by PQT3 for targeted degradation via 26S proteasome. Therefore, we have identified PQT3 as an E3 ligase that acts as a negative regulator of activated response to oxidative stress and found that histone modification by PRMT4b at APX1 and GPX1 loci plays an important role in oxidative stress tolerance.