N-6-methyladenosine (m6A) promotes the nuclear retention of mRNAs with intact 5' splice site motifs.

ABSTRACT: In humans, misprocessed mRNAs containing intact 5' Splice Site (5'SS) motifs are nuclear retained and targeted for decay by ZFC3H1, a component of the Poly(A) Exosome Targeting complex, and U1-70K, a component of the U1 snRNP. In S. pombe, the ZFC3H1 homolog, Red1, binds to the YTH domain-containing protein Mmi1 and targets certain RNA transcripts to nuclear foci for nuclear retention and decay. Here we show that YTHDC1 and YTHDC2, two YTH domain-containing proteins that bind to N-6-methyladenosine (m6A) modified RNAs, interact with ZFC3H1 and U1-70K, and are required for the nuclear retention of mRNAs with intact 5'SS motifs. Disruption of m6A deposition inhibits both the nuclear retention of these transcripts and their accumulation in YTHDC1-enriched foci that are adjacent

SUBMITTER: Lee ES 

PROVIDER: S-EPMC11629677 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature