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Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.

ABSTRACT: Contrary to the membrane-anchored leukemia inhibitory factor receptor (LIFR), the mouse soluble LIFR is an inhibitor of LIF action, possibly through a ligand titration effect. Two mRNA species encoding the soluble LIFR have been identified. Since the 3'-untranslated end of the shorter form was shown to contain a B2 element, we have examined the possibility that this SINE may be responsible for LIFR mRNA truncation. Transient expression assays, using B2-derived or intron-derived sequences independently or in conjunction, show that the B2 element has fortuitously unmasked a cryptic pre-mRNA 3'processing activity of silent intron sequences. The corresponding locus of the rat genome has been isolated and was shown to be devoid of any retroposon, which may explain why no soluble LIFR has yet been identified in any other species and further indicates that the B2 insertion event in the mouse LIFR gene has occurred recently during evolution. And yet, a tight tissue-specific regulation of alternative synthesis of soluble and membrane-bound LIFR mRNA has already emerged in mice. These results provide striking evidence for the rapid influence of retroposition on genome expression.

SUBMITTER: Michel D

PROVIDER: S-EPMC146886 | biostudies-other | 1997 Aug

REPOSITORIES: biostudies-other

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Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.

Michel D D Chatelain G G Mauduit C C Benahmed M M Brun G G

Nucleic acids research 19970801 16

Contrary to the membrane-anchored leukemia inhibitory factor receptor (LIFR), the mouse soluble LIFR is an inhibitor of LIF action, possibly through a ligand titration effect. Two mRNA species encoding the soluble LIFR have been identified. Since the 3'-untranslated end of the shorter form was shown to contain a B2 element, we have examined the possibility that this SINE may be responsible for LIFR mRNA truncation. Transient expression assays, using B2-derived or intron-derived sequences indepen ...[more]

PMID: 9241235

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Project description:Many alternative splicing events are regulated by pentameric and hexameric intronic sequences that serve as binding sites for splicing regulatory factors. We hypothesized that intronic elements that regulate alternative splicing are under selective pressure for evolutionary conservation. Using a Wobble Aware Bulk Aligner genomic alignment of Caenorhabditis elegans and Caenorhabditis briggsae, we identified 147 alternatively spliced cassette exons that exhibit short regions of high nucleotide conservation in the introns flanking the alternative exon. In vivo experiments on the alternatively spliced let-2 gene confirm that these conserved regions can be important for alternative splicing regulation. Conserved intronic element sequences were collected into a dataset and the occurrence of each pentamer and hexamer motif was counted. We compared the frequency of pentamers and hexamers in the conserved intronic elements to a dataset of all C. elegans intron sequences in order to identify short intronic motifs that are more likely to be associated with alternative splicing. High-scoring motifs were examined for upstream or downstream preferences in introns surrounding alternative exons. Many of the high-scoring nematode pentamer and hexamer motifs correspond to known mammalian splicing regulatory sequences, such as (T)GCATG, indicating that the mechanism of alternative splicing regulation is well conserved in metazoans. A comparison of the analysis of the conserved intronic elements, and analysis of the entire introns flanking these same exons, reveals that focusing on intronic conservation can increase the sensitivity of detecting putative splicing regulatory motifs. This approach also identified novel sequences whose role in splicing is under investigation and has allowed us to take a step forward in defining a catalog of splicing regulatory elements for an organism. In vivo experiments confirm that one novel high-scoring sequence from our analysis, (T)CTATC, is important for alternative splicing regulation of the unc-52 gene.

Dataset Information

Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.

Publications

Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.

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