YTHDC1 phase separation drives the nuclear export of m⁶A-modified lncNONMMUT062668.2 through the transport complex SRSF3-ALYREF-XPO5 to aggravate pulmonary fibrosis.

ABSTRACT: Fibroblast-to-myofibroblast differentiation is the main cytopathologic characteristic of pulmonary fibrosis. However, its underlying molecular mechanism remains poorly understood. This study elucidated that the nuclear export of lncNONMMUT062668.2 (lnc668) exacerbated pulmonary fibrosis by activating fibroblast-to-myofibroblast differentiation. Mechanistic research revealed that histone H3K9 lactylation in the promoter region of the N6-methyladenosine (m⁶A) writer METTL3 was enriched to enhance METTL3 transcription, leading to the lnc668 m⁶A modification. Meanwhile, the m⁶A reader YTHDC1 recognized m⁶A-modified lnc668 and elevated the METTL3-mediated lnc668 modification. Subsequently, phase-separating YTHDC1 promoted the nuclear export of m⁶

SUBMITTER: Chen S 

PROVIDER: S-EPMC11993731 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature