Diverse roles of hnRNP L in mammalian mRNA processing: A combined microarray and RNAi analysis
Diverse roles of hnRNP L in mammalian mRNA processing: A combined microarray and RNAi analysis
复制标题
DOI：
10.1261/rna.725208
复制
发表时间：
2008-02-01
期刊：
影响因子：
4.5
通讯作者：
Bindereif, Albrecht
中科院分区：
文献类型：
--
作者：
Hung, Lee-Hsueh;Heiner, Monika;Bindereif, Albrecht
可选择的mRNA剪接模式由调节蛋白及其靶RNA序列的组合控制决定。我们最近将人类hnRNP L描述为选择性剪接的全球调节因子，与多种富含C/ a的元素结合。为了在全基因组水平上系统地鉴定hnRNP - L靶基因，我们结合了剪接敏感微阵列分析和rnai敲低方法。因此，我们描述了11个经RT-PCR验证的hnRNP L靶基因，它们代表了hnRNP L依赖性剪接调控的几种新模式，涉及激活子和抑制子功能：首先，内含子保留；第二，盒式外显子的包含或跳过；第三，抑制多个外显子；第四，备选聚(A)的选址。总之，这种方法揭示了剪接调控过程的惊人多样性以及hnRNP L参与的聚(a)位点选择。
Alternative mRNA splicing patterns are determined by the combinatorial control of regulator proteins and their target RNA sequences. We have recently characterized human hnRNP L as a global regulator of alternative splicing, binding to diverse C/A-rich elements. To systematically identify hnRNP L target genes on a genome-wide level, we have combined splice-sensitive microarray analysis and an RNAi-knockdown approach. As a result, we describe 11 target genes of hnRNP L that were validated by RT-PCR and that represent several new modes of hnRNP L-dependent splicing regulation, involving both activator and repressor functions: first, intron retention; second, inclusion or skipping of cassette-type exons; third, suppression of multiple exons; and fourth, alternative poly(A) site selection. In sum, this approach revealed a surprising diversity of splicing-regulatory processes as well as poly(A) site selection in which hnRNP L is involved.