small-scale-nuclear-extracts-for-functional-assays-gene-expression

Small-scale Nuclear Extracts for Functional Assays of Gene-expression Machineries

A great deal of progress in understanding gene expression has been made using in vitro systems.  For most studies, functional assays are carried out using ...

Duplex formation between the branch point-binding region (BBR) of U2 snRNA and the branch point sequence (BPS) in the intron is essential for splicing. Both the BBR and BPS interact with the U2 small nuclear ribonucleoprotein (snRNP)-associated SF3b complex, which is the target of the anti-tumor drug E7107. We show that E7107 blocks spliceosome assembly by preventing tight binding of U2 snRNP to pre-mRNA. E7107 has no apparent effect on U2 snRNP integrity. Instead, E7107 abolishes an ATP-dependent conformational change in U2 snRNP that exposes the BBR. We conclude that SF3b is required for this remodeling, which exposes the BBR for tight U2 snRNP binding to pre-mRNA.

The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region.

Duplex Bildung zwischen der Verzweigung Punkt-Bindung Region (BBR) U2 SnRNA und der Verzweigung Punkt Sequenz (BPS) in der Intron ist wesentlich f&uuml;r das Splei&szlig;en. BBR sowohl die BPS interagieren mit kleinen nuklearen Ribonucleoprotein U2 (SnRNP)-assoziierten SF3b Komplex, das ist das Ziel der Anti-Tumor-Wirkstoff E7107. Wir zeigen diese E7107 Bl&ouml;cke Spliceosom Assembly durch enge Bindung der U2 SnRNP zur Pre-mRNA verhindern. E7107 hat keinen offensichtlichen Effekt auf U2 SnRNP Integrit&auml;t. Stattdessen schafft E7107 eine ATP-abh&auml;ngigen Konformations&auml;nderungen Ver&auml;nderung U2 SnRNP, die die BBR verf&uuml;gbar macht. Wir schlie&szlig;en, dass die SF3b f&uuml;r diesen Umbau, erforderlich ist, die Macht der BBR f&uuml;r die engen U2 SnRNP Bindung an Pre-mRNA verf&uuml;gbar.

Das Anti-Tumor-Medikament E7107 offenbart eine wesentliche Rolle f&uuml;r SF3b im Umbau U2 SnRNP um die Verzweigung Punkt-Bindung Region verf&uuml;gbar zu machen.

Die somatische genetische Basis von chronischer lymphatischer Leuk&auml;mie, eine gemeinsame und klinisch heterogene Leuk&auml;mie bei Erwachsenen auftretenden bleibt weitgehend unverstanden.

SF3B1 und andere neue Krebstherapien-Gene in chronischer lymphatischer Leuk&auml;mie.

The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood.

Article	Year
Cell\| PubMed ID: 11909523	2002
Nature\| PubMed ID: 11932736	2002
Nature\| PubMed ID: 11979277	2002
Biochimica et biophysica acta\| PubMed ID: 12084575	2002
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 12215496	2002
Nature\| PubMed ID: 12226669	2002
Molecular pharmacology\| PubMed ID: 12527807	2003
Current opinion in cell biology\| PubMed ID: 12787775	2003
Protein expression and purification\| PubMed ID: 12963337	2003
Cell\| PubMed ID: 14718168	2004
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 14769921	2004
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 15024115	2004
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 15753297	2005
Current opinion in cell biology\| PubMed ID: 15901496	2005
Genes & development\| PubMed ID: 15998806	2005
Eukaryotic cell\| PubMed ID: 16151247	2005
Genes & development\| PubMed ID: 16651655	2006
Human mutation\| PubMed ID: 16964593	2007
Cell\| PubMed ID: 17190602	2006
Journal of molecular medicine (Berlin, Germany)\| PubMed ID: 17206408	2007
Blood\| PubMed ID: 17475909	2007
Molecular cell\| PubMed ID: 17588520	2007
Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.]\| PubMed ID: 18265328	2003
Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.]\| PubMed ID: 18265329	2003
Current protocols in molecular biology / edited by Frederick M. Ausubel ... [et al.]\| PubMed ID: 18265330	2003
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 18287003	2008
Nucleic acids research\| PubMed ID: 18628297	2008
Nucleic acids research\| PubMed ID: 20631007	2010
Genes & development\| PubMed ID: 20844015	2010
Nature communications\| PubMed ID: 20981025	2010
The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region. Genes & development\| PubMed ID: 21363962	2011
Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 22010220	2011
SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. The New England journal of medicine\| PubMed ID: 22150006	2011
Psychiatric services (Washington, D.C.)\| PubMed ID: 22549541	2012

Robin Reed

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