Genome-wide identification of alternatively spliced mRNA targets of specific RNA-binding proteins.
Genome-wide identification of alternatively spliced mRNA targets of specific RNA-binding proteins.
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DOI：
10.1371/journal.pone.0000520
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发表时间：
2007-06-13
期刊：
影响因子：
3.7
通讯作者：
Singh, Ravinder
中科院分区：
文献类型：
--
作者：
Robida, Mark D.;Rahn, Andrew;Singh, Ravinder
选择性剪接在多细胞生物体中产生分子和功能多样性方面起着重要作用。RNA结合蛋白在调节剪接位点选择中起着至关重要的作用。大多数已知的调节蛋白的结合位点是短的、简并的共有序列，其在整个基因组中频繁出现。这对区分功能相关序列和大量偶然发生的序列提出了重要挑战。在这里，我们已经使用了一种计算方法，结合了一系列的生物学约束，以确定尿苷丰富的序列基序，存在于相关的生物背景下，因此是潜在的目标的果蝇主性别开关蛋白性致死（SXL）。这一策略导致了一个新的目标的确定。此外，我们的系统分析提供了一个起点的分子和功能特性的额外的目标，这是依赖于SXL的活动，直接或间接，在一个生殖系特异性的方式进行调节。这种方法已经成功地确定了以前已知的，新的和潜在的SXL目标。我们的分析表明，只有一个子集的潜在SXL网站的监管SXL。最后，这种方法应该是直接相关的绝大多数剪接调节蛋白的真正的目标是未知的。
Alternative splicing plays an important role in generating molecular and functional diversity in multi-cellular organisms. RNA binding proteins play crucial roles in modulating splice site choice. The majority of known binding sites for regulatory proteins are short, degenerate consensus sequences that occur frequently throughout the genome. This poses an important challenge to distinguish between functionally relevant sequences and a vast array of those occurring by chance. Here we have used a computational approach that combines a series of biological constraints to identify uridine-rich sequence motifs that are present within relevant biological contexts and thus are potential targets of the Drosophila master sex-switch protein Sex-lethal (SXL). This strategy led to the identification of one novel target. Moreover, our systematic analysis provides a starting point for the molecular and functional characterization of an additional target, which is dependent on SXL activity, either directly or indirectly, for regulation in a germline-specific manner. This approach has successfully identified previously known, new, and potential SXL targets. Our analysis suggests that only a subset of potential SXL sites are regulated by SXL. Finally, this approach should be directly relevant to the large majority of splicing regulatory proteins for which bonafide targets are unknown.
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DOI：
10.1016/s0167-4781(97)00213-3
发表时间：
1998-04-29
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Eisen, A;Sattah, M;Lucchesi, J
通讯作者：
Lucchesi, J
影响因子：
11.4
作者：
Fujii, S;Amrein, H
通讯作者：
Amrein, H
影响因子：
11.4
作者：
KANAAR, R;LEE, AL;RIO, DC
通讯作者：
RIO, DC
影响因子：
30.8
作者：
Manak, J. Robert;Dike, Sujit;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
影响因子：
3.3
作者：
Hicks, JL;Deng, WM;Bownes, M
通讯作者：
Bownes, M