mRNA association by aminoacyl tRNA synthetase occurs at a putative anticodon mimic and autoregulates translation in response to tRNA levels.

Abstract:

:Aminoacyl-tRNA synthetases (aaRSs) are well studied for their role in binding and charging tRNAs with cognate amino acids. Recent RNA interactome studies had suggested that these enzymes can also bind polyadenylated RNAs. Here, we explored the mRNA repertoire bound by several yeast aaRSs. RNA immunoprecipitation (RIP) followed by deep sequencing revealed unique sets of mRNAs bound by each aaRS. Interestingly, for every tested aaRSs, a preferential association with its own mRNA was observed, suggesting an autoregulatory process. Self-association of histidyl-tRNA synthetase (HisRS) was found to be mediated primarily through binding to a region predicted to fold into a tRNAHis anticodon-like structure. Introducing point mutations that are expected to disassemble this putative anticodon mimic alleviated self-association, concomitant with increased synthesis of the protein. Finally, we found that increased cellular levels of uncharged tRNAHis lead to reduced self-association and increased HisRS translation, in a manner that depends on the anticodon-like element. Together, these results reveal a novel post-transcriptional autoregulatory mechanism that exploits binding mimicry to control mRNA translation according to tRNA demands.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Levi O,Arava Y

doi

10.1371/journal.pbio.3000274

subject

Has Abstract

pub_date

2019-05-17 00:00:00

pages

e3000274

issue

5

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-18-01096

journal_volume

17

pub_type

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