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Research Topics in Physiology course (#7190, 3 credits):

     In this course, we are going to discuss a series of original research papers that cover a variety of questions in regulated alternative splicing, including splicing changes by external stimulation[1,2] or during differentiation[3], influence from the transcriptional machinery[4], constitutive splicing factors targeted[5-7], changes in spliceosomes[8], a regulatory factor binding to different splice sites[9], regulation of splicing factors by microRNAs or autoregulation[10-12], identification of global splicing changes upon stimulation in exon array[13], and splicing in diseases[14]. One topic will be discussed each week.
     After each session's discussion about the paper(s), a one page essay is due on the following Monday morning. The essay should include at least a summary of the paper, critical comments and the most recent progress. After all the sessions, a final essay reviewing the whole field is due within 2 weeks.  Forty percent of the final score will be from the final essay.

List of the papers to be discussed:

Sessions
 Research Papers
I
 1. Matter N, Herrlich P, Konig H: Signal-dependent regulation of splicing via phosphorylation of Sam68. Nature 2002, 420:691-695.
2. Shin C, Feng Y, Manley JL: Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 2004, 427:553-558.
II
 3. Oberdoerffer S, Moita LF, Neems D, Freitas RP, Hacohen N, Rao A: Regulation of CD45 alternative splicing by heterogeneous ribonucleoprotein, hnRNP LL. Science 2008, 321:686-691.
III
 4. McCracken S, Fong N, Yankulov K, Ballantyne S, Pan G, Greenblatt J, Patterson SD, Wickens M, Bentley DL: The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 1997, 385:357-361.

IV
 5. Wu S, Romfo CM, Nilsen TW, Green MR: Functional recognition of the 3' splice site AG by the splicing factor U2AF35. Nature 1999, 402:832-835.
6. Zorio DAR, Blumenthal T: Both subunits of U2AF recognize the 3' splice site in Caenorhabditis elegans. Nature (London) 1999, 402:835-838.
7. Merendino L, Guth S, Bilbao D, Martinez C, Valcarcel J: Inhibition of msl-2 splicing by Sex-lethal reveals interaction between U2AF35 and the 3' splice site AG. Nature (London) 1999, 402:838-841.8. 
V
 8. Sharma S, Falick AM, Black DL: Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex. Mol Cell 2005, 19:485-496.
VI
 9. Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, Zhang C, Yeo G, Black DL, Sun H, et al.: Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping. Mol Cell 2009, 36:996-1006.
VII
 10. Boutz PL, Chawla G, Stoilov P, Black DL: MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev 2007, 21:71-84.
11. Spellman R, Llorian M, Smith CW: Crossregulation and functional redundancy between the splicing regulator PTB and its paralogs nPTB and ROD1. Mol Cell 2007, 27:420-434.
12. Makeyev EV, Zhang J, Carrasco MA, Maniatis T: The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 2007, 27:435-448.
VIII
 13. McKee AE, Neretti N, Carvalho LE, Meyer CA, Fox EA, Brodsky AS, Silver PA: Exon expression profiling reveals stimulus-mediated exon use in neural cells. Genome Biol 2007, 8:R159.
IX
 14. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, et al.: Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998, 393:702-705.
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