%0 Journal Article
%T Alternative Splicing Regulation of Cancer-Related Pathways in Caenorhabditis elegans: An In Vivo Model System with a Powerful Reverse Genetics Toolbox
%A Sergio Barber¨˘n-Soler
%A James Matthew Ragle
%J International Journal of Cell Biology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/636050
%X Alternative splicing allows for the generation of protein diversity and fine-tunes gene expression. Several model systems have been used for the in vivo study of alternative splicing. Here we review the use of the nematode Caenorhabditis elegans to study splicing regulation in vivo. Recent studies have shown that close to 25% of genes in the worm genome undergo alternative splicing. A big proportion of these events are functional, conserved, and under strict regulation either across development or other conditions. Several techniques like genome-wide RNAi screens and bichromatic reporters are available for the study of alternative splicing in worms. In this review, we focus, first, on the main studies that have been performed to dissect alternative splicing in this system and later on examples from genes that have human homologs that are implicated in cancer. The significant advancement towards understanding the regulation of alternative splicing and cancer that the C. elegans system has offered is discussed. 1. Introduction Since the early 1960s with the efforts of Sydney Brenner, the nematode Caenorhabditis elegans has been established as a popular model organism in developmental biology and neurobiology. There are many biological advantages that make it an attractive system for several fields of research. The adult worm contains 959 somatic cells, making its anatomy relatively simple. Experiments in the late 1970s showed that it has an invariant cell lineage during establishment of the somatic tissues [1]. It has two sexes, a self-fertilizing hermaphrodite and males, allowing genetic crosses to be performed. C. elegans has a short life cycle of less than three days and each hermaphrodite produces about 300 progeny by self-fertilization or up to 1000 progeny from cross progeny with males. The gonad is a relatively large organ in this animal, allowing for studies of organogenesis, cell proliferation, meiosis, and embryogenesis. During its development, the hermaphrodite worms produce sperm at one stage of their life cycle before switching to produce oocytes. The molecular pathways of this sperm to oocyte transition have been studied extensively [2]. Its complete genome, sequenced in 1998, was the first sequenced genome from a multicellular organism. It has a genome size of 97 megabases containing close to 19,000 protein coding genes [3]. Genome-wide alignments with other five related nematodes are now available for any comparative genomics approach [4]. The modENCODE project systematically generated genome-wide data from transcriptome profiling,
%U http://www.hindawi.com/journals/ijcb/2013/636050/