Control of mRNA stability by anti-decapping and mRNA granules
Description: The stability of mRNA plays a key role in controlling and shaping gene expression. Central players in this process are cytoplasmic ribonucleoprotein (mRNPs) foci termed RNA granules. Archetypes of these RNA granules are cytoplasmic processing bodies (P bodies), which are concentrated sites of non-translating mRNA, mRNA decay intermediates, proteins involved in translation repression and mRNA decay factors, most notably the mRNA decapping enzyme, which is essential for rapid mRNA degradation. Our previous research has revealed a central role for RNA granules in mRNA metabolism. In this proposal, we aim to further extend our studies in two main areas: First, we explore the mechanism of an anti-decapping factor in decreasing mRNA stability globally that we have identified. Supporting this, we obtained genome-wide transcription, mRNA stability and abundance data suggesting that a mutation in the Lsm4 protein, previously believed to be an activator of mRNA decapping, is instead an anti-decapping factor. We propose to examine its mechanism of anti-decapping action. Second, we examine the role of RNA granules and mRNA stability adaptation to stress, starvation and aging. Taken together, these experiments are directed toward understanding when, why and how mRNA is degraded, and the importance of mRNA degradation and mRNA granules for survival under stress.
Funder: Vetenskapsrådet
Amount: SEK 3,125,000
Funding type: research
Funder scheme: Project grant
Start date: 2018-01-01
End date: 2021-12-31
Investigator: Tracy Nissan
Institution: Stockholm University
Funded outputs count: 10
Funder award ID: 2017-04663
OpenAlex ID: G3676896440