Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2 SINE insertion.
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.
Michel
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Laboratoire de Biologie Moléculaire et Cellulaire, UMR49 CNRS-Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon cedex 07, France. denis.michel@univ-rennes1.fr
Chatelain
G
G
Mauduit
C
C
Benahmed
M
M
Brun
G
G
D017398:Alternative Splicing; D001483:Base Sequence; D005075:Biological Evolution; D005091:Exons; D005786:Gene Expression Regulation; D005796:Genes; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015850:Interleukin-6; D007438:Introns; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008969:Molecular Sequence Data; D012322:RNA Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D018121:Receptors, Cytokine / Q000235:genetics*; D053606:Receptors, OSM-LIF; D012091:Repetitive Sequences, Nucleic Acid; D012995:Solubility; D014018:Tissue Distribution; D014158:Transcription, Genetic
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; C507842:Lifr protein, rat; D008222:Lymphokines; D012322:RNA Precursors; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF