當(dāng)人類基因組被解碼時(shí),，科學(xué)家發(fā)現(xiàn)基因數(shù)量比他們預(yù)計(jì)的要少，這重新激發(fā)了他們對選擇性剪接（從一個(gè)基因產(chǎn)生一個(gè)以上蛋白的一種機(jī)制）的興趣,。
Licatalosi等人研究出一種對活組織中的RNA–蛋白結(jié)合相互作用進(jìn)行定性的不帶偏見的,、涉及整個(gè)基因組的方法，并且通過將該方法應(yīng)用于哺乳動物大腦而顯示了其潛力,。他們對神經(jīng)選擇性剪接調(diào)控因子Nova的結(jié)合點(diǎn)進(jìn)行了定性,，并且獲得了意想不到的發(fā)現(xiàn)：該調(diào)控因子也許在調(diào)控選擇性多腺苷酸化中還有另一種功能。在另一項(xiàng)研究中,，Wang等人利用對mRNAs的深度測序來研究不同人組織和癌癥中的選擇性剪接,。通過將序列數(shù)據(jù)與剪接點(diǎn)進(jìn)行比對,，他們發(fā)現(xiàn),，選擇性剪接在人類多外顯子基因中實(shí)質(zhì)上是普遍現(xiàn)象。他們還發(fā)現(xiàn),，選擇性剪接與mRNA多腺苷酸化在機(jī)制上有聯(lián)系,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 456, 464-469 (27 November 2008) | doi:10.1038/nature07488
HITS-CLIP yields genome-wide insights into brain alternative RNA processing
Donny D. Licatalosi1, Aldo Mele1, John J. Fak1, Jernej Ule3, Melis Kayikci3, Sung Wook Chi1, Tyson A. Clark4, Anthony C. Schweitzer4, John E. Blume4, Xuning Wang2, Jennifer C. Darnell1 & Robert B. Darnell1
1 Laboratory of Molecular Neuro-Oncology and Howard Hughes Medical Institute,
2 Biocomputing, Information Technology, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
3 MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK
4 Expression Research, Affymetrix, Inc., Santa Clara, California 95051, USA
Protein–RNA interactions have critical roles in all aspects of gene expression. However, applying biochemical methods to understand such interactions in living tissues has been challenging. Here we develop a genome-wide means of mapping protein–RNA binding sites in vivo, by high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova revealed extremely reproducible RNA-binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova–RNA interactions in 3' untranslated regions, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein–RNA interactions in vivo.
