Kim, Iktae Bang, Kyeong-Mi An, So Young Park, Changkon Shin, Ji-Yeon Kim, Youngim Song, Hyun Kyu Suh, Jeong-Yong Kim, Nak-Kyoon 2025-11-21T02:16:34Z 2025-11-21T02:16:34Z 2025-11-11 2026-03 1742-464X https://pubs.kist.re.kr/handle/201004/153592 Human spliceosome-associated factor 3, SART3, is a key factor in spliceosome recycling and engages with U6 small nuclear RNA (snRNA) to promote the formation of the U4/U6 small nuclear ribonucleoprotein complex. Unlike its counterpart U4/U6 snRNA-associated-splicing factor PRP24 (Prp24) from Saccharomyces cerevisiae, which uses four RNA recognition motifs (RRMs) for the U6 snRNA interaction, SART3 has two RRMs at its C terminus. Here, we demonstrate that SART3 binds U6 snRNA as a dimer, and four RRM subunits recognize the asymmetric bulge of U6 snRNA. SART3 RRMs adopt a tandem βαββαβ motif of the canonical RRM fold to interact with the U6 bulge region via a conserved electropositive surface. We identified the cognate U6 elements that specifically bind SART3 RRM1, which is distinct from the Prp24–U6 interactions in yeast. Our findings suggest a divergent RRM binding mechanism for U6 snRNA recognition during spliceosome assembly and recycling. English Blackwell Publishing Inc. Structural investigation of human U6 snRNA recognition by spliceosomal recycling factor SART3 RNA recognition motifs Article 10.1111/febs.70275 1 FEBS Journal, v.293, no.5, pp.1323 - 1340 FEBS Journal 293 5 1323 1340 Y scie scopus 2-s2.0-105018331887 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article; Early Access CHEMICAL-SHIFTS FACTOR P110 NMR PROTEIN ANGLES RNA recognition motif SART3 solution structure U6 snRNA