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Originally published in Science Express on 11 September 2003
Science 10 October 2003:
Vol. 302. no. 5643, pp. 279 - 282
DOI: 10.1126/science.1086602
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Reports

The Prp19p-Associated Complex in Spliceosome Activation

Shih-Peng Chan,1,2 Der-I Kao,2 Wei-Yü Tsai,1,2* Soo-Chen Cheng1,2{dagger}

During spliceosome activation, a large structural rearrangement occurs that involves the release of two small nuclear RNAs, U1 and U4, and the addition of a protein complex associated with Prp19p. We show here that the Prp19p-associated complex is required for stable association of U5 and U6 with the spliceosome after U4 is dissociated. Ultraviolet crosslinking analysis revealed the existence of two modes of base pairing between U6 and the 5' splice site, as well as a switch of such base pairing from one to the other that required the Prp19p-associated complex during spliceosome activation. Moreover, a Prp19p-dependent structural change in U6 small nuclear ribonucleoprotein particles was detected that involves destabilization of Sm-like (Lsm) proteins to bring about interactions between the Lsm binding site of U6 and the intron sequence near the 5' splice site, indicating dynamic association of Lsm with U6 and a direct role of Lsm proteins in activation of the spliceosome.

1 Institute of Microbiology and Immunology, National Yang-Ming University, Shih-Pai, Taiwan, Republic of China.
2 Institute of Molecular Biology, Academia Sinica, Nankang, Taiwan, Republic of China.



* Present address: School of Medical Technology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.

{dagger} To whom correspondence should be addressed. E-mail: mbscc{at}ccvax.sinica.edu.tw

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