{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:09:08Z","timestamp":1770498548442,"version":"3.49.0"},"reference-count":74,"publisher":"Cold Spring Harbor Laboratory","issue":"14","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1998,7,15]]},"abstract":"<jats:p>The SR proteins constitute a family of splicing factors, highly conserved in metazoans, that contain one or two amino-terminal RNA-binding domains (RBDs) and a region enriched in arginine\/serine repeats (RS domain) at the carboxyl terminus. Previous studies have shown that SR proteins possess distinct RNA-binding specificities that likely contribute to their unique functions, but it is unclear whether RS domains have specific roles in vivo. Here, we used a genetic system developed in the chicken B cell line DT40 to address this question. Expression of chimeric proteins generated by fusion of the RS domains of heterologous SR proteins, or a human TRA-2 protein, with the RBDs of ASF\/SF2 allowed cell growth following genetic inactivation of endogenous ASF\/SF2, indicating that RS domains are interchangeable for all functions required to maintain cell viability. However, a chimera containing the RS domain from a related splicing factor, U2AF<jats:sup>65<\/jats:sup>, could not rescue viability and was inactive in in vitro splicing assays, suggesting that this domain performs a distinct function. We also used the DT40 system to show that depletion of ASF\/SF2 affects splicing of specific transcripts in vivo. Although splicing of several simple constitutive introns was not significantly affected, the alternative splicing patterns of two model pre-mRNAs switched in a manner consistent with predictions from previous studies. Unexpectedly, ASF\/SF2 depletion resulted in a substantial increase in splicing of an HIV-1 tat pre-mRNA substrate, indicating that ASF\/SF2 can repress tat splicing in vivo. These results provide the first demonstration that an SR protein can influence splicing of specific pre-mRNAs in vivo.<\/jats:p>","DOI":"10.1101\/gad.12.14.2222","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:52:17Z","timestamp":1203547937000},"page":"2222-2233","source":"Crossref","is-referenced-by-count":71,"title":["Genetic analysis of the SR protein ASF\/SF2: interchangeability of RS domains and negative control of\u2009splicing"],"prefix":"10.1101","volume":"12","author":[{"given":"Jin","family":"Wang","sequence":"first","affiliation":[]},{"given":"Shou-Hua","family":"Xiao","sequence":"additional","affiliation":[]},{"given":"James L.","family":"Manley","sequence":"additional","affiliation":[]}],"member":"246","published-online":{"date-parts":[[1998,7,15]]},"reference":[{"key":"2021111418551295000_12.14.2222.1","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1128\/MCB.15.8.4606","article-title":"Presence of exon splicing silencers within human immunodeficiency virus type 1 tat exon 2 and tat-rev exon 3: Evidence for inhibition mediated by cellular factors.","volume":"15","author":"Amendt","year":"1995","journal-title":"Mol. 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