YTHDC1

YTHDC1 (YTH domain-containing protein 1) is a human protein encoded by the YTHDC1 gene. It is a member of the YTH family of RNA-binding proteins that recognize N6-methyladenosine (m6A), a common internal modification of eukaryotic mRNA and certain long noncoding RNAs. In contrast to cytoplasmic YTH readers, YTHDC1 is primarily localized in the nucleus where it engages with nascent transcripts and RNA-processing factors.

The protein contains a YTH domain that forms a hydrophobic pocket recognizing m6A-modified RNA. This domain mediates selective binding to methylated transcripts, enabling YTHDC1 to influence RNA metabolism through processing steps occurring in the nucleus rather than transcription initiation alone.

Functionally, YTHDC1 participates in m6A-dependent pre-mRNA processing. It associates with splicing factors such as SRSF3 to influence alternative splicing and can modulate the activity of other splicing regulators to shape exon inclusion. YTHDC1 also participates in the nuclear export of m6A-containing transcripts by engaging with the TREX export machinery and the mRNA export receptor NXF1, guiding methylated messages from the nucleus to the cytoplasm.

Biological significance includes involvement in gene expression programs during development and differentiation in model systems. Its expression and activity are being investigated for links to disease, including cancer, where altered m6A reading by YTH family proteins may affect RNA processing. As a nuclear m6A reader, YTHDC1 complements cytoplasmic YTH readers to coordinate post-transcriptional regulation of RNA.