Is the capture of RNA by RNase E and not its cleavage the major initiator of mRNA turnover?

Lead Research Organisation: University of Leeds
Department Name: Inst of Molecular & Cellular Biology

Abstract

E. coli RNase E is a major regulator of gene expression and homologues are found in many bacteria and plant plastids. In a series of landmark papers published this year, we have shown that contrary to current models RNase E can survey multiple sites directly without being constrained by 5'-end tethering. We have also outlined the underlying mechanism. This work, which has important ramifications, was funded by the BBSRC and featured on their website.
Objectives: In addition to the above, we have made a finding that may produce a seismic shift in our understanding of gene regulation. We have found that RNase E reaches beyond the RNA it cleaves and binds to virtually any it encounters. The broad objective of this project is to establish whether the binding of 5' untranslated regions (UTRs) by RNase E represents a major route by which translation is regulated in E. coli. The specific aims are to (1) confirm that RNase E binds to many 5' UTRs with high affinity, (2) establish that binding of 30S ribosomal subunits can be outcompeted by RNase E, and (3) determine the overall influence of RNase E binding on translation.
Novelty: The hypothesis is novel. Never before has it been proposed that RNase E, or indeed any other ribonuclease, can regulate translation by outcompeting ribosomes for binding to 5' UTRs. Moreover, the inactivation of mRNAs before the first cleavage could prevent the futile and perhaps deleterious translation of partially degraded transcripts. Our most recent direct entry paper was published as a "Breakthrough" article and was given the front cover.
Timeliness: The proposed project not only comes on the back of a series of strong publications plus recent findings that were unexpected and unprecedented, it fits with major initiatives in synthetic biology and the development of new antibiotics.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1647923 Studentship BB/M011151/1 30/09/2015 29/09/2019 Jaskiran Sabharwal