Dissecting the sequence and structural determinants guiding m6A deposition and evolution via inter- and intra-species hybrids.

ABSTRACT:

Background

N6-methyladenosine (m6A) is the most abundant mRNA modification, and controls mRNA stability. m6A distribution varies considerably between and within species. Yet, it is unclear to what extent this variability is driven by changes in genetic sequences ('cis') or cellular environments ('trans') and via which mechanisms.

Results

Here we dissect the determinants governing RNA methylation via interspecies and intraspecies hybrids in yeast and mammalian systems, coupled with massively parallel reporter assays and m6A-QTL reanalysis. We find that m6A evolution and variability is driven primarily in 'cis', via two mechanisms: (1) variations altering m6A consensus motifs, and (2) variation impacting mRNA secondary structure. We establish that mutations impacting RNA struc

SUBMITTER: Shachar R 

PROVIDER: S-EPMC10870504 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature