title: An exonic splicing silencer represses spliceosome assembly after ATP-dependent exon recognition.
abstract: Precursor messenger RNA splicing is catalyzed by the spliceosome, a macromolecular complex that assembles in a stepwise process. The spliceosome's dynamic nature suggests the potential for regulation at numerous points along the assembly pathway; however, thus far, naturally occurring regulation of splicing has only been found to influence a small subset of spliceosomal intermediates. Here we report that the exonic splicing silencer (ESS1) that represses splicing of PTPRC (encoding CD45) exon 4 does not function by the typical mechanism of inhibiting binding of U1 or U2 small nuclear ribonucleoproteins (snRNPs) to the splice sites. Instead, a U1-, U2- and ATP-dependent complex forms across exon 4 that is required for inhibiting progression to the U4-U6-U5 tri-snRNP-containing B complex. Such inhibition represents a new mechanism for splicing regulation and suggests that regulation can probably occur at many of the transitions along the spliceosome assembly pathway.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: House
authors.forename: Kristen W
authors.initials: KW
authors.lastname: Lynch
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000737:chemistry; D017493:Leukocyte Common Antigens / Q000235:genetics; D008954:Models, Biological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D017411:Ribonucleoproteins, Small Nuclear / Q000737:chemistry; D037941:Silencer Elements, Transcriptional; D017381:Spliceosomes / Q000378:metabolism*
chemical_list: D034441:Heterogeneous-Nuclear Ribonucleoproteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D017411:Ribonucleoproteins, Small Nuclear; D000255:Adenosine Triphosphate; D017493:Leukocyte Common Antigens; D019696:Peptidylprolyl Isomerase