RECENT EVOLUTIONARY ACQUISITION OF ALTERNATIVE PRE-MESSENGER-RNA 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 solu ble LIFR have been identified. Since the S'-untranslated end of the sh orter form was shown to contain a B2 element, vie have examined the po ssibility that this SINE may be responsible for LIFR mRNA truncation. Transient expression assays, using BP-derived or intron-derived sequen ces independently or in conjunction, show that the B2 element has fort uitously unmasked a cryptic pre-mRNA 3' processing activity of silent intron sequences. The corresponding locus of the rat genome has been i solated and was shown to be devoid of any retroposon, which may explai n why no soluble LIER 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-specif ic regulation of alternative synthesis of soluble and membrane-bound L IFR mRNA has already emerged in mice. These results provide striking e vidence for the rapid influence of retroposition on genome expression.