title: SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles.
abstract: The mammalian cell nucleus is compartmentalized into nonmembranous subnuclear domains that regulate key nuclear functions. Nuclear speckles are subnuclear domains that contain pre-mRNA processing factors and noncoding RNAs. Many of the nuclear speckle constituents work in concert to coordinate multiple steps of gene expression, including transcription, pre-mRNA processing and mRNA transport. The mechanism that regulates the formation and maintenance of nuclear speckles in the interphase nucleus is poorly understood. In the present study, we provide evidence for the involvement of nuclear speckle resident proteins and RNA components in the organization of nuclear speckles. SR-family splicing factors and their binding partner, long noncoding metastasis-associated lung adenocarcinoma transcript 1 RNA, can nucleate the assembly of nuclear speckles in the interphase nucleus. Depletion of SRSF1 in human cells compromises the association of splicing factors to nuclear speckles and influences the levels and activity of other SR proteins. Furthermore, on a stably integrated reporter gene locus, we demonstrate the role of SRSF1 in RNA polymerase II-mediated transcription. Our results suggest that SR proteins mediate the assembly of nuclear speckles and regulate gene expression by influencing both transcriptional and posttranscriptional activities within the cell nucleus.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Vidisha
authors.initials: V
authors.lastname: Tripathi
authors.forename: David Y
authors.initials: DY
authors.lastname: Song
authors.forename: Xinying
authors.initials: X
authors.lastname: Zong
authors.forename: Sergey P
authors.initials: SP
authors.lastname: Shevtsov
authors.forename: Stephen
authors.initials: S
authors.lastname: Hearn
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu
authors.forename: Miroslav
authors.initials: M
authors.lastname: Dundr
authors.forename: Kannanganattu V
authors.initials: KV
authors.lastname: Prasanth
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012326:RNA Splicing; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism; D000068103:Serine-Arginine Splicing Factors; D014158:Transcription, Genetic
chemical_list: D008164:Luminescent Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors; D012319:RNA Polymerase II