Molecular Biology Select

Recent work provides new insights into the regulation of fertility in animals, plants, and unicellular eukaryotes. These findings suggest that fertility is controlled by the dynamic and complex interplay of numerous factors including the regulation of RNA stability, protein translation, chromatin structure, and chromosomal organization. In a recent study, Chu et al. (2006) sought factors that are important for male fertility in the nematode Caenorhabditis elegans. They compared an extensive set of proteins that copurify with chromatin from C. elegans sperm with a similar set of proteins that copurify with chromatin from oocytes. To determine the identity of the copurifying proteins, the authors used a variation of mass spectrometry called MudPIT (multidimensional protein identification technology), which is well-suited for the large-scale analysis of proteins in complex mixtures. This comparison yielded a list of 132 proteins that are enriched in preparations of sperm chromatin. Reducing the expression of each of these genes encoding the 132 proteins by RNA interference showed that 38% of gene knockdowns resulted in decreased fertility in C. elegans. Furthermore , of these 132 proteins, 29 have homologs that have been knocked out in mice. When deleted, one third of these proteins cause a male sterility phenotype in the respective mouse knockout. As further validation for their approach, human homologs of two of the C. elegans proteins have reported links to male infertility. These human homologs are topoisomerase I, which could have a role in DNA condensation or during spermatogenesis, and DBY, a VASA RNA helicase found in a region of the Y chromosome that is frequently deleted in infertile men. Although the Chu et al. study primarily characterized proteins related to spermatogenesis, the approach also yielded a list of 444 proteins that are specifically enriched on oocyte chromatin. Undoubtedly, this study will also serve as a starting point in the search for new factors that specifically affect fertility in females. MIWI is a mouse member of the PIWI/Argonaute family of proteins. These proteins bind to a new class of small RNAs called piRNAs (PIWI-interacting RNAs) that are approximately 30 nucleotides in length. Although the function of MIWI is unclear, mice lacking MIWI have defects in spermatogenesis. Building on earlier studies, Grivna et al. (2006) now report that MIWI is intimately associated with the translation machinery. They find that MIWI associates with ribonu-cleoprotein particles and with cytosolic ribosomes, including both monosomes and polysomes. Interestingly, most MIWI molecules are …