Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing

Area of Science:

• Molecular Biology
• RNA Biology
• Epigenetics

Background:

• The function of N(6)-methyladenosine (m(6)A) and its reader protein YTHDC1 in pre-mRNA splicing is not well understood.
• m(6)A is a prevalent RNA modification impacting various cellular processes.

Purpose of the Study:

• To elucidate the regulatory mechanism of YTHDC1 in pre-mRNA splicing.
• To investigate the interaction between YTHDC1 and splicing factors SRSF3 and SRSF10.

Main Methods:

• Transcriptome-wide analysis using PAR-CLIP-seq.
• In vitro pull-down assays.
• Nuclear speckle localization studies.

Main Results:

• YTHDC1 promotes exon inclusion by recruiting SRSF3 and inhibiting SRSF10 binding.
• YTHDC1-mediated splicing patterns mirror SRSF3 but oppose SRSF10.
• YTHDC1 influences the localization and RNA-binding of SRSF3 and SRSF10.

Conclusions:

• YTHDC1 acts as an m(6)A reader to modulate mRNA splicing.
• YTHDC1 directly regulates splicing factors, impacting their access to target mRNAs.
• This study provides direct evidence for YTHDC1's role in splicing regulation.