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EURODYNA 2004-03: Cell biology of messenger RNA biogenesis

English title EURODYNA 2004-03: Cell biology of messenger RNA biogenesis
Applicant Keller Walter
Number 108705
Funding scheme Project funding (special)
Research institution Abteilung Zellbiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Cellular Biology, Cytology
Start/End 01.01.2005 - 31.03.2009
Approved amount 378'425.00
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All Disciplines (2)

Discipline
Cellular Biology, Cytology
Molecular Biology

Keywords (7)

mRNA biogenesis; messenger RNA; RNA processing; mRNA polyadenylation; poly(A) polymerase; 3' end formation; RNA splicing

Lay Summary (English)

Lead
Lay summary
We are working on the biochemical and genetic characterization of the protein machinery involved in the processing of messenger RNA precursors (pre-mRNAs) in the nucleus of eukaryotic cells. Pre-mRNAs are synthesized by RNA polymerase II and undergo three processing steps that include the addition of a 7-methyl guanosine "cap" at the 5' end, the removal of intron sequences by RNA splicing and the addition of a poly(A) tail at their 3' ends. The cap and the poly(A) tails have multiple functions. In the nucleus they interact with a complex of cap binding proteins and with a nuclear form of poly(A) binding protein and thereby signal to the RNA export machinery that they are ready to be transported to the cytoplasm. In the cytoplasm they interact with a different set of proteins and form circular mRNAs by interactions between the proteins bound to the cap and the cytoplasmic version of the the poly(A) binding protein. Circularization serves to protect the mRNAs against premature degradation and increases the efficiency of their translation into proteins.In collaboration with Professor Bernhard Dichtl (University of Zürich) we have investigated the coupling of different RNA processing reactions and RNA transcription in yeast. By a combination of genetic and biochemical analyses we have found that the cleavage and polyadenylation factor subunit Ysh1p has multiple functions. In addition to its role in cleavage and polyadenylation it is involved in cleavage site selection and in transcription termination of messenger RNAs and small nucleolar RNAs. A function of Ysh1p in the coupling of pre-mRNAsplicing and 3' end processing is possible but has not yet been conclusively demonstrated. In collaboration with the laboratory of Dr. André Gerber (ETH Zürich) we have carried out a genome wide analysis of the expression of the non-canonical poly(A) polymerases Trf4p and Trf5p, which are components of the so-called TRAMP complexes that degrade aberrant and short-lived RNAs in the budding yeast S. cerevisiae. Trf4p and Trf5p are alternative subunits of these complexes that add short poly(A) tails to their substrate RNAs that function as landing pads for exonucleases mediating RNA decay. Applying a genome-wide approach, we found overlapping yet distinct functional specificities of TRAMP complexes, and we demonstrated strong connections between RNA quality control and other RNA-related processes such as telomer length maintenance. Moreover, it appears that the degradation of specific target RNAs is not strictly dependent on the polyadenylation activity of Trf proteins in vivo.
Direct link to Lay Summary Last update: 21.02.2013

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