To the pore and through the pore: A story of mRNA export kinetics

Faculty of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec, Canada H3A 1A3.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 02/2012; 1819(6):494-506. DOI: 10.1016/j.bbagrm.2012.02.011
Source: PubMed


The evolutionary 'decision' to store genetic information away from the place of protein synthesis, in a separate compartment, has forced eukaryotic cells to establish a system to transport mRNAs from the nucleus to the cytoplasm for translation. To ensure export to be fast and efficient, cells have evolved a complex molecular interplay that is tightly regulated. Over the last few decades, many of the individual players in this process have been described, starting with the composition of the nuclear pore complex to proteins that modulate co-transcriptional events required to prepare an mRNP for export to the cytoplasm. How the interplay between all the factors and processes results in the efficient and selective export of mRNAs from the nucleus and how the export process itself is executed within cells, however, is still not fully understood. Recent advances in using proteomic and single molecule microscopy approaches have provided important insights into the process and its kinetics. This review summarizes these recent advances and how they led to the current view on how cells orchestrate the export of mRNAs. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.

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Available from: Marlene Oeffinger, Feb 11, 2014
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    • "NPCs consist of more than two dozen different proteins [132]. These nucleoporins form a channel and regulate the nucleocytoplasmic transport of various types of RNAs [133], and proteins [134]. The nuclear import and export of most proteins >40 KDa in size, including membrane "
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    • "Nuclear mRNP assembly initiates with the cotranscriptional recruitment of mRNA processing factors and several other mRNA-associated proteins, some of which are acting as adaptors for the mRNA-export machinery (2). In budding yeast, Yra1, Nab2 and Npl3 serve as adaptors for the Mex67-Mtr2 export receptor, which ultimately brings mRNPs to the nuclear pore complex (NPC) through interaction with nucleoporins (3). In addition, cotranscriptional mRNP assembly has been shown to involve THO, which is a conserved tetrameric complex comprised of four subunits in yeast—Tho2, Hpr1, Mft1 and Thp2 (4). "
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    • "Transport is powered by a gradient of GDP-versus GTP-bound Ran, a small Ras-like GTPase (Grossman et al., 2012). Export of mRNA, in some systems at least, utilises non-KAP factors, including Mex67, and is Ran-independent (Oeffinger & Zenklusen, 2012). There are differences in molecular mechanisms of nucleocytoplasmic transport between yeast, plants and mammals, and specifically in how the Ran gradient is controlled; in metazoa, RanGAP activity (GAPs stimulate GTPase activity converting the GTPase from a GTP to GDP-bound form) is associated with the nuclear pore complex, but in A. thaliana the RanGAP is targeted to the nuclear envelope by nuclear envelopeembedded trans-membrane domain proteins (Meier et al., 2007; Xu et al., 2007), while in S. cerevisiae RanGAP is not targeted to the nuclear envelope at all. "
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