Connecting Neurotransmitter Signaling to RNA Splicing

Abstract

Ania-6a is a novel cyclin (see Nairn and Greengard) that is most similar to those cyclins involved in RNA processing, as opposed to cell-cycle regulation. Berke et al . show that expression of the two alternative splice variants of Ania-6a can be independently induced by different neurotransmitters: Dopamine induces expression of both the long and short form, glutamate induces only the short form. The shorter transcript actually encodes a longer form of the protein, which contains in the COOH-terminal region an arginine-serine (RS) domain and three nuclear localization signals. The long Ania-6a protein localizes to nuclear speckles, subnuclear compartments that are the site of RNA splicing, and localizes with highly phosphorylated RNA polymerase II (Pol IIo). An interaction between long Ania-6a and Pol IIo, the splicing factor SC-35, and the orphan cyclin p110 PITSLRE (which is also found in nuclear speckles and interacts with components of the splicing machinery and Pol IIo) was also found. Thus, long Ania-6a may be one link between dopamine signaling and acute regulation of splicing that could be involved in neural plasticity events. For more information on the regulation of alternative splicing see the Meeting Report by Cooper and the Perspectives by O'Donovan and Darnell and by Finkbeiner . A. C. Nairn, P. Greengard, A novel cyclin provides a link between dopamine and RNA processing. Neuron 32 , 174-176 (2001). [Online Journal] J. D. Berke, V. Sgambato, P.-P. Zhu, B. Lavoie, M. Vincent, M. Krause, S. E. Hyman, Dopamine and glutamate induce distinct striatal splice forms of ania-6, an RNA polymerase II-associated cyclin. Neuron 32 , 277-287 (2001). [Online Journal] T. A. Cooper, Highlights of alternative splicing regulation session: Yes, no, maybe--A history of paradigm shifts. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/105/pe35. [Abstract] [Full Text] K. J. O'Donovan, R. B. Darnell, Neuronal signaling through alternative splicing: Some exons CaRRE.... Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/94/pe2. [Abstract] [Full Text] S. Finkbeiner, New roles for introns: Sites of combinatorial regulation of Ca 2+ - and cyclic AMP-dependent gene transcription. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/94/pe1. [Abstract] [Full Text]