GENOME-WIDE IDENTIFICATION OF RNA SENSORS IN PROKARYOTES AND EUKARYOTES

Tez Türü: Doktora

Tezin Yürütüldüğü Kurum: National University of Singapore, Biyokimya, Singapur

Tez Danışmanı: Huck Hui Ng & Yue Wan

Tezin Onay Tarihi: 2019

Tezin Dili: Türkçe

Desteklendiği Program: Diğer

Özet:

RNA's ability to fold into complex secondary and tertiary structures underlies its suitability as cellular sensors that detect and respond to metabolite changes in the environment. Much remains to be learnt about the diversity and distributions of RNA sensors in prokaryotes and eukaryotes. Current approaches for identifying them rely heavily on detecting homology to a small, experimentally validated set in silico. Here, we introduce a high-throughput strategy named PARCEL that directly and experimentally identifies RNA sensors genome-wide. Applying PARCEL to a collection of prokaryotic and eukaryotic organisms revealed 58 novel RNA sensors, expanding the list of known RNA sensors to key metabolites. Concordant with their functional roles, the newly identified RNA sensors exhibit significant sequence and structure conservation, but an unexpected prevalence outside of non-coding regions and with new structural motifs. We identified a precursor tmRNA that acts as an RNA sensor for FMN to facilitate tmRNA maturation. We also discovered an entirely new class of eukaryotic RNA sensors that recognize vitamin B2 (FMN), demonstrating that FMN sensing can impact eukaryotic gene translation. This collection of RNA sensors expands our understanding of RNA function in the cell and suggests that RNA based sensing and gene regulation is much more widespread than previously appreciated