Trafficking of RNA and protein between the nucleus and cytoplasm is essential to cell viability and it must be both efficient and well-controlled. The process of RNA export presents an opportunity to check th integrity of the products of transcription and processing, prior to their export to the cytoplasm. The applicant proposes that proofreading is a key feature in the export of RNAs. RNAs or RNPs that are present in excessive quantities, or that are defective as a consequence of mutation or incomplete o incorrect processing, are hypothesized to be retained and then degraded in the nucleus. To learn how various types of RNAs are exported from the nucleus and what features contributes to their proofreading, three specific aims will be pursued. These are: (1) to study the mechanisms by which tRNAs are exported an to determine what features of tRNAs are necessary and sufficient for their export; (2) to study the mechanisms by which the constitutive transport elemen (CTE) of MPMV is able to promote the release of incompletely spliced pre-mRNAs from spliceosomes and to relate export of that element to the process of norma mRNA export; and (3) to study the structure of a small RNA export element identified in a screen for exportable RNAs and determine what factors lead to its export or retention. For most of the experiments, Xenopus laevis oocytes will be used as a model system to identify and study transport factors, but some studies involve genetic selections in yeast. The focus will be on the structure and functions of cis-acting signals in RNA, their interactions with specific RNA export factors, and the mechanisms by which these factors promote export.
| Lund, Elsebet; Liu, Mingzhu; Hartley, Rebecca S et al. (2009) Deadenylation of maternal mRNAs mediated by miR-427 in Xenopus laevis embryos. RNA 15:2351-63 |
| Eis, Peggy S; Garcia-Blanco, Mariano A (2008) Quantification of microRNAs, splicing isoforms, and homologous mRNAs with the invader assay. Methods Mol Biol 488:279-318 |
| Lund, E; Dahlberg, J E (2006) Substrate selectivity of exportin 5 and Dicer in the biogenesis of microRNAs. Cold Spring Harb Symp Quant Biol 71:59-66 |
| Eis, Peggy S; Tam, Wayne; Sun, Liping et al. (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A 102:3627-32 |
| Lund, Elsebet; Guttinger, Stephan; Calado, Angelo et al. (2004) Nuclear export of microRNA precursors. Science 303:95-8 |
| Dahlberg, James E; Lund, Elsebet (2004) Does protein synthesis occur in the nucleus? Curr Opin Cell Biol 16:335-8 |
| Allawi, Hatim T; Dahlberg, James E; Olson, Sarah et al. (2004) Quantitation of microRNAs using a modified Invader assay. RNA 10:1153-61 |
| Trotta, Christopher R; Lund, Elsebet; Kahan, Lawrence et al. (2003) Coordinated nuclear export of 60S ribosomal subunits and NMD3 in vertebrates. EMBO J 22:2841-51 |
| Dahlberg, James E; Lund, Elsebet; Goodwin, Elizabeth B (2003) Nuclear translation: what is the evidence? RNA 9:1-8 |
| Glodowski, Doreen R; Petersen, Jeannine M; Dahlberg, James E (2002) Complex nuclear localization signals in the matrix protein of vesicular stomatitis virus. J Biol Chem 277:46864-70 |
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