Bio 525 (Spring 2012)
Current Topics on mRNA export.
Instructor: Dr. Michael C. Yu
Jan. 16, 2012-Feb. 6, 2012 (MWF, 9:00AM – 10:50AM)

This section of Bio 525 takes an in-depth look at current understanding in the field of mRNA export. This course is a literature-based course in which participants are expected to present and dissect primary literatures that aid our understanding of mRNA export – how it is achieved and what are the outstanding questions in this field. In addition, how mRNA export contributes to other aspects of RNA metabolism within a cell will be discussed. The grade you will receive will be based on your presentations (partially given by your peers and partially given by your instructor) and participations throughout the class (questions, discussions, etc).

The order of presentation will be assigned at the beginning of the class, and there will be a one-week recess prior to the start of the first presentation. Everyone is EXPECTED to have read the paper being presented that day and participate in discussion.

For a quick recap on how to give “journal club” type presentations, a file is accompanied that provide some “pointers”.

Reading list:
Reviews:
Cole & Scarcelli, 2006, “Transport of messenger RNA from the nucleus to the cytoplasm”
Darzacq, X. et al, 2005, “Dynamics of transcription and mRNA export”
Aguilera, A., 2005, “Cotranscriptional mRNP assembly: from the DNA to the nuclear pore”
Kelly and Corbett, 2009, “Messenger RNA export from the nucleus: a series of molecular wardrobe changes”
Taura, T et al, 2005 “The Molecular Mechanisms of mRNA Export”
Rodriguez-Navarro & Hurt, 2011, “Linking Gene Regulation to mRNA Production and Export”

Methods:
Chakraborty, P. et al, 2006 “Nuclear export assays for poly(A) RNAs”

Research Articles:
**see the dates below for all of the primary articles to presented by class participants in this class. Each person will present 2 articles (on different dates)

Course Schedule:
1/16/2012
Assigning papers for presentation – overview of the class

1/18/2012
General overview of the topics on mRNA export

• Purpose for mRNA export in an eukaryotic cell
• Model Systems Used: Pros & Cons
• mRNP biogenesis: building specificity
• Surveillance: snipping out the wrong message
• Exporting the message
• Common/Recent Techniques used to dissect mRNA export

1/23/2012
Players in mRNA export: hnRNPs
“A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway”
Michael, W.M., Choi, M., and Dreyfuss, G.
Cell. 1995 83, 415-422.

“A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export”
Lee MS, Henry M, Silver PA.
Genes Dev. 1996 May 15;10(10):1233-46.

Connecting transcription with mRNA export:
“TREX is a conserved complex coupling transcription with mRNA export”
Strässer K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondón AG, Aguilera A, Struhl K, Reed R, Hurt E.
Nature. 2002 May 16;417(6886):304-8.

1/25/2012
Co-transcriptional processing facilitates mRNP Assembly & export
“Messenger RNAs are recruited for nuclear export during transcription”
Lei EP, Krebber H, Silver PA.
Genes Dev. 2001 Jul 15;15(14):1771-82.

Relevant News & Views: “Choreographing mRNA biogenesis” by Cole CN.
Nat Genet. 2001 Sep;29(1):6-7.

“The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay”
Le Hir H, Gatfield D, Izaurralde E, Moore MJ.
EMBO J. 2001 Sep 3;20(17):4987-97.

Achieving mRNA export specificity & regulation
“Genome-wide analysis of RNA-protein interactions illustrates specificity of the mRNA export machinery”
Hieronymus H, Silver PA.
Nat Genet. 2003 Feb;33(2):155-61. Epub 2003 Jan 13.

Relevant News & Views: “Organizing mRNA export” by Keene, JD.
Nat Genet. 2003 Feb;33(2):155-61.

1/27/2012
“Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export”
Krebber H, Taura T, Lee MS, Silver PA.
Genes Dev. 1999 Aug 1;13(15):1994-2004.

“TRA-1 regulates the cellular distribution of the tra-2 mRNA in C. elegans”
Graves LE, Segal S, Goodwin EB.
Nature. 1999 Jun 24;399(6738):802-5.

The role of post-translational modification in mRNA export
“Ubiquitin-mediated mRNP dynamics and surveillance prior to budding yeast mRNA export”
Iglesias N, Tutucci E, Gwizdek C, Vinciguerra P, Von Dach E, Corbett AH, Dargemont C, and Stutz F.
Genes Dev. 2010. 24:1927-1938

1/30/2012
Interplay between mRNA export, transcription, and nuclear pore
“THO/Sub2p functions to coordinate 3'-end processing with gene-nuclear pore association”
Rougemaille M, Dieppois G, Kisseleva-Romanova E, Gudipati RK, Lemoine S, Blugeon C, Boulay J, Jensen TH, Stutz F, Devaux F, Libri D.
Cell. 2008 Oct 17;135(2):308-21.

Relevant News & Views: “Nuclear roadblocks for mRNA export” by Rondon, AG. and Proudfoot NJ.
Cell. 2008. Oct 17; 135(2):207-8

Connecting nucleoporins to gene regulation
“Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes”
Capelson M, Liang Y, Schulte R, Mair W, Wagner U, Hetzer MW.
Cell. 2010 Feb 5;140(3):372-83.

“Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm”
Kalverda B, Pickersgill H, Shloma VV, Fornerod M.
Cell. 2010 Feb 5;140(3):360-71.

2/1/2012
Information specifying the export of mRNAs?
“The signal sequence coding region promotes nuclear export of mRNA”
Palazzo AF, Springer M, Shibata Y, Lee CS, Dias AP, Rapoport TA. PLoS
Biol. 2007 Dec;5(12):e322.

Surveillance: check point for faulty messages
“Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export”
Vinciguerra P, Iglesias N, Camblong J, Zenklusen D, Stutz F.
EMBO J. 2005 Feb 23;24(4):813-23. Epub 2005 Feb 3.

End of Export?
“The DEAD-box protein Dbp5p is required to dissociate Mex67p from exported mRNPs at the nuclear rim”
Lund MK, Guthrie C.
Mol Cell. 2005 Nov 23;20(4):645-51.

2/3/2012
End of Export (Con’t)
“The DEAD-box protein Dbp5 controls mRNA export by triggering specific RNA:protein remodeling events”
Tran EJ, Zhou Y, Corbett AH, Wente SR.
Mol Cell. 2007 Dec 14;28(5):850-9.

Linking mRNA export to translational control
“The mRNA export factor Gle1 and inositol hexakisphosphate regulate distinct stages of translation”
Bolger TA, Folkmann AW, Tran EJ, and Wente SR
Cell. 2008. 134:624-633

“The DEAD-box RNA helicase Dbp5 functions in translation termination”
Gross T, Siepmann A, Sturm D, Windgassen M, Scarcelli JJ, Seedorf M, Cole CN, Krebber H
Science. 2007. 315:646-649