RNA Processing Marches on

Western General Hospital generates different forms of the mRNA and functionally Crewe Road different proteins. This is accomplished by modulation Edinburgh EH4 2XU of the basic splicing mechanism, frequently involving changes in the relative activities of antagonistic factors. Key players are the SR protein family. These consist of Introduction one or two RNA-recognition motifs (RRMs) plus a C-ter-The regulation of gene expression is one of the key minal, arginine-serine rich (RS) domain, reversible phos-activities in all organisms; however, the extent to which phorylation of which regulates their activity. SR proteins this regulation occurs at the posttranscriptional level show functional redundancy in constitutive splicing but has only recently been appreciated. Activities as diverse have unique functions in regulating alternative splicing. Edinburgh) reported that the SR protein CeSF2/ASF is learning, among many others are regulated by RNA essential in C. elegans; whereas RNAi of other SR genes processing, often in tissue-and developmentally spe-resulted in no obvious phenotype (Longman et al., 2000). cific patterns, and are regulated by a variety of signaling The activity of SR proteins in alternative splicing is pathways. Some of these topics were explored during antagonized by members of the hnRNP A/B family of a meeting held at the Juan March Foundation in Madrid nuclear pre-mRNA binding proteins. Stress induces from 2 to 4 October 2000, entitled " Regulation of Mes-hnRNP A1 phosphorylation by a p38-MAP kinase path-senger RNA Processing. " way (van der Houven van Oordt et al., 2000) and relocal-ization to the cytoplasm. The decrease in the nuclear Choosing the Site hnRNP A1 to SR protein ratio influences alternative In metazoans, the synthesis of most mRNAs requires splice site selection. Thus, signal transduction pathways the removal of intervening sequences, or introns, from can control alternative splicing regulation by affecting the pre-mRNA by the process of splicing. Splicing oc-the subcellular localization of splicing factors. curs within a large macromolecular complex, the Gö ran Akusjä rvi (Uppsala U.) reported that adenovirus spliceosome, which contains the U1, U2, and U4/5/6 also modulates SR protein phosphorylation to regulate small nuclear ribonucleoprotein particles (snRNPs), to-alternative splicing. Early in infection, phosphorylated gether with many other splicing factors. SF2/ASF binds to an intronic purine-rich sequence in Metazoan genes typically contain short exons sepa-the adenovirus major late transcript and inhibits splicing rated by introns that can be kilobases or megabases in at the distal 3Ј splice site IIIa. Late in infection, the viral length. Drosophila …