Much attention has focused on biological regulation through control of gene transcription. But control mechanisms don't stop there, and new evidence is accumulating that suggests that extensive interactions between proteins and mRNAs provide posttranscriptional mechanisms for controlling translation of RNAs to protein. Gerber et al. conducted a genome-wide search for mRNAs that associated with PUMILIO (Pum), an RNA binding protein from Drosophila. Pum and related proteins in yeast were already known to function in a broad range of biological processes, particularly in development. These range from anterior-posterior patterning in the fly embryo--which results in part through control of the abundance of a key transcription factor--to germ cell development and neuronal development and function. However, only a handful of target mRNAs have been identified. That is no longer a problem, as the authors' screen, in which RNAs that associated with an affinity-tagged fragment of Pum were identified after conversion to fluorescently tagged cDNA probes and hybridization to a DNA microarray, yielded on the order of 1000 mRNAs from adult tissue that showed specific association with Pum. These included the interactors known from traditional forward genetic studies. Similar analysis of material from embryos yielded a couple hundred different interactors. Even allowing for the usual caveats regarding false-positive and false-negative results of such methods, the screen appears to substantially expand the reach of the biological effects of Pum. Exploration of the gene ontology annotations for functions of the sequences identified showed enrichment for mRNAs involved in nucleotide metabolism and transcriptional regulation and transcripts localized to organelle membranes. In the embryo samples, Pum appeared to associate preferentially with regulators of axis formation. The authors suggest that the results with Pum argue for "a highly organized and multifaceted posttranscriptional regulatory system in multicellular organisms."
A. P. Gerber, S. Luschnig, M. A. Krasnow, P. O. Brown, D. Herschlag, Genome-wide identification of mRNAs associated with the translational regulator PUMILIO in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 103, 4487-4492 (2006). [Abstract] [Full Text]