RNA Select

RNAs are versatile molecules capable of an array of functions. In addition to their role as information-carrying intermediaries in gene expression, they act as key catalytic, structural, and regulatory elements in the cell. As highlighted in this issue's Select, recent studies on RNA show how these molecules collaborate with proteins in essential biological processes such as pre-mRNA splicing, mRNA export, and translation control. Additionally, new findings reveal that RNAs can act as enzymes in an efficient, protein-free, self-sustained RNA replication system, providing further support for the notion that life could have originated from an RNA-based world. Spatial restriction of protein synthesis can affect cell fate outcomes during development and contribute to the formation of subcellular compartments in differentiated cells. A number of mRNA transcripts are known to be locally translated, including the oskar transcript of the fruit fly Drosophila. However, the mechanisms that ensure localized translation remain unclear. Oskar mRNAs are locally translated during Drosophila oogenesis. The mRNAs are transported to specific sites in the developing oocyte and maintained in a transla-tionally repressed state until translation is activated. To gain insight into how oskar mRNAs are spatially and temporally regulated, Besse et al. performed a screen using a green fluorescent protein (GFP)-based ''protein trap'' to identify proteins that colocalize with oskar mRNA. The screen uses a transposable element to randomly tag proteins with GFP. Using this approach, they found that the polypyrimidine tract-binding protein (PTB) colocalizes with oskar. Experiments with ptb mutants revealed that PTB is required for proper timing of oskar localization and translation. Furthermore, native gel electrophoresis and RNA affinity pull-down assays showed that PTB binds directly to the oskar 3 0 untranslated region (UTR). PTB binding mediates oligomerization of oskar mRNA into high-order complexes that could be observed by electron microscopy. This work reveals yet another role for the multifunctional PTB protein, which is also involved in pre-mRNA splicing and cap-independent translation initiation of messages containing internal ribosome entry sites. The work also suggests that multimerization of oskar mRNA into ribonu-cleoprotein (RNP) complexes may repress translation by reducing the accessibility of the mRNA to the translation machinery. If DNA is required to make proteins and proteins are required to make DNA, then how were the first proteins made and how was genetic information propagated in early life? RNA may provide answers to these questions because, like DNA, it can carry genetic information and, like proteins, it is …