Figure 2 | m6
A-dependent mRNA processing promotes translation and decay,
and affects splicing. a | After being deposited by the methyltransferase core
catalytic components methyltransferase-like 3 (METTL3) and METTL14,
N6
-methyladenosine (m6
A) is recognized by various reader proteins. In the nucleus,
heterogeneous nuclear ribonucleoprotein C (HNRNPC) functions as an indirect m6
A
reader by binding unstructured m6
A switch regions and regulating splicing, whereas
YT521‑B homology (YTH) domain-containing 1 (YTHDC1) regulates alternative
splicing by binding m6
A directly and recruiting the splicing factors serine and
arginine-rich splicing factor 3 (SRSF3) while blocking binding by SRSF10. HNRNPA2B1
also mediates alternative splicing in a manner similar to YTHDC1. In the cytoplasm,
YTHDF1 mediates translation initiation of m6
A-containing transcripts by binding
directly to m6
A and recruiting eukaryotic initiation factor 3 (eIF3), thereby facilitating
the loading of the eukaryotic small ribosomal subunit (40S). YTHDF2 promotes mRNA
decay by binding to CCR4–NOT transcription complex subunit 1 (CNOT1), thereby
facilitating the recruitment of the CCR4–NOT complex and inducing accelerated
deadenylation. b|Methylated transcripts may be sorted by reader proteins into a
fast track (right) for processing, translation and decay. This fast-tracking effectively
groups transcripts with otherwise markedly different properties to ensure their timely
and coordinated translation and degradation, possibly generating a sharp ‘pulse’ of
gene expression to satisfy a need for translational bursts and subsequent clearance
of these transcripts.