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Recent evolutionary acquisition of alternative pre-mRNA splicing and 3' processing regulations induced by intronic B2
D Michel1, G Chatelain, C Mauduit
1Laboratoire 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
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.
Insights
Mouse soluble leukemia inhibitory factor receptor (LIFR) inhibits LIF action. A B2 SINE element in LIFR mRNA unexpectedly activated cryptic intron splicing, leading to soluble LIFR. This highlights rapid retroposition
Area of Science:
- Molecular Biology
- Genomics
- Gene Regulation
Background:
- Leukemia inhibitory factor receptor (LIFR) exists in membrane-bound and soluble forms.
- Soluble LIFR acts as an inhibitor of LIF signaling, potentially via ligand titration.
- Two mRNA species for soluble LIFR have been identified in mice.
Purpose of the Study:
- To investigate the role of a B2 SINE element in the 3'-untranslated region of shorter LIFR mRNA.
- To determine if the B2 element is responsible for LIFR mRNA truncation.
- To understand the evolutionary origin and regulation of soluble LIFR expression.
Main Methods:
- Transient expression assays using B2-derived and intron-derived sequences.
- Isolation and characterization of the corresponding rat genomic locus.
- Analysis of alternative mRNA synthesis in mice.
Main Results:
- The B2 element unmasked cryptic 3' processing activity in silent intron sequences, leading to mRNA truncation.
- The rat LIFR locus lacks retroposons, suggesting a recent B2 insertion event in the mouse.
- Mice exhibit tight tissue-specific regulation of alternative soluble and membrane-bound LIFR mRNA synthesis.
Conclusions:
- Retroposition of B2 elements can rapidly influence genome expression by creating novel mRNA variants.
- The unmasking of cryptic splicing by SINEs provides a mechanism for generating functional diversity.
- The findings demonstrate rapid evolutionary adaptation driven by retrotransposon activity.