title: C. elegans sequences that control trans-splicing and operon pre-mRNA processing.
abstract: Many mRNAs in Caenorhabditis elegans are generated through a trans-splicing reaction that adds one of two classes of spliced leader RNA to an independently transcribed pre-mRNA. SL1 leaders are spliced mostly to pre-mRNAs from genes with outrons, intron-like sequences at the 5'-ends of the pre-mRNAs. In contrast, SL2 leaders are nearly exclusively trans-spliced to genes that occur downstream in polycistronic pre-mRNAs produced from operons. Operon pre-mRNA processing requires separation into individual transcripts, which is accomplished by 3'-processing of upstream genes and spliced leader trans-splicing to the downstream genes. We used a novel computational analysis, based on nonnegative matrix factorization, to identify and characterize significant differences in the cis-acting sequence elements that differentiate various types of functional site, including internal versus terminal 3'-processing sites, and SL1 versus SL2 trans-splicing sites. We describe several key elements, including the U-rich (Ur) element that couples 3'-processing with SL2 trans-splicing, and a novel outron (Ou) element that occurs upstream of SL1 trans-splicing sites. Finally, we present models of the distinct classes of trans-splicing reaction, including SL1 trans-splicing at the outron, SL2 trans-splicing in standard operons, competitive SL1-SL2 trans-splicing in operons with large intergenic separation, and SL1 trans-splicing in SL1-type operons, which have no intergenic separation.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA. joel.graber@jax.org
authors.forename: Joel H
authors.initials: JH
authors.lastname: Graber
authors.forename: Jesse
authors.initials: J
authors.lastname: Salisbury
authors.forename: Lucie N
authors.initials: LN
authors.lastname: Hutchins
authors.forename: Thomas
authors.initials: T
authors.lastname: Blumenthal
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008957:Models, Genetic; D009876:Operon / Q000502:physiology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D022821:RNA Splice Sites / Q000235:genetics*; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism*; D020038:RNA, Spliced Leader / Q000235:genetics / Q000378:metabolism; D020040:Trans-Splicing / Q000502:physiology*
chemical_list: D012322:RNA Precursors; D022821:RNA Splice Sites; D018510:RNA, Helminth; D020038:RNA, Spliced Leader