title: Dephosphorylation-dependent sorting of SR splicing factors during mRNP maturation.
abstract: SR proteins are a family of sequence-specific RNA binding proteins originally discovered as essential factors for pre-mRNA splicing and recently implicated in mRNA transport, stability, and translation. Here, we used a genetic complementation system derived from conditional knockout mice to address the function and regulation of SR proteins in vivo. We demonstrate that ASF/SF2 and SC35 are each required for cell viability, but, surprisingly, the effector RS domain of ASF/SF2 is dispensable for cell survival in MEFs. Although shuttling SR proteins have been implicated in mRNA export, prevention of ASF/SF2 from shuttling had little impact on mRNA export. We found that shuttling and nonshuttling SR proteins are segregated in an orderly fashion during mRNP maturation, indicating distinct recycling pathways for different SR proteins. We further showed that this process is regulated by differential dephosphorylation of the RS domain, thus revealing a sorting mechanism for mRNP transition from splicing to export.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors.forename: Shengrong
authors.initials: S
authors.lastname: Lin
authors.forename: Ran
authors.initials: R
authors.lastname: Xiao
authors.forename: Peiqing
authors.initials: P
authors.lastname: Sun
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Xu
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D012326:RNA Splicing / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D012261:Ribonucleoproteins; C499372:SRSF2 protein, mouse; D000068103:Serine-Arginine Splicing Factors