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Article Abstract
The lncRNA silences gene expression by recruiting the protein SPEN through its 5'-proximal Repeat A domain. How Repeat A recruits SPEN, how SPEN enacts silencing, and why Repeat A is required for biogenesis in addition to silencing remain unclear. We find that sequences in Repeat A critical for SPEN recruitment, silencing, and biogenesis directly bind SR-rich splicing factors and not SPEN. SRSF1, one such factor, is necessary and sufficient for SPEN recruitment to Repeat A. SPEN and SR protein-binding motifs in Repeat A enable 's association with many proteins, including those involved in m A methylation, RNA turnover, and transcriptional elongation. Our results reveal an unexpectedly essential role for splicing factors in coordinating silencing by SPEN and suggest a unifying model for the origin of Repeat A, the function of SPEN, and their roles in biogenesis and silencing.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154583 | PMC |
| http://dx.doi.org/10.1101/2025.05.21.655143 | DOI Listing |
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