The C-terminal domain of RNA Pol II helps ensure that editing precedes splicing of the GluR-B transcript.
The C-terminal domain of RNA Pol II helps ensure that editing precedes splicing of the GluR-B transcript.
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DOI：
10.1261/rna.404407
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发表时间：
2007-07
期刊：
影响因子：
4.5
通讯作者：
Kicki Ryman;N. Fong;Eva Bratt;D. Bentley;M. Ohman
中科院分区：
文献类型：
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作者：
Kicki Ryman;N. Fong;Eva Bratt;D. Bentley;M. Ohman
RNA聚合酶II （Pol II）大亚基的c端结构域（CTD）影响mRNA合成的许多步骤，并有助于控制成熟转录物的最终命运。ADAR2通过在双链或结构化RNA中将腺苷转化为肌苷来编辑RNA。位点选择性A-to-I编辑通常发生在外显子/内含子边界附近的位点，在那里它依赖于内含子序列来识别底物。因此，编辑在拼接之前是必要的。我们已经研究了ADAR2的编辑和GluR-B pre-mRNA的剪接之间是否存在协调。我们发现CTD是在5'-剪接位点上游一个碱基的R/G位点进行有效编辑所必需的。结果表明，CTD通过防止过早剪接来增强R/G位点的编辑，过早剪接会去除ADAR2的内含子识别位点。在GluR-B Q/R位点（位于内含子115 '-剪接位点上游24个碱基）进行编辑，会刺激该内含子的剪接。此外，与先前研究的内含子不同，CTD实际上抑制内含子11的切除，内含子11包括Q/R编辑位点的互补识别序列。综上所述，这些结果表明CTD和ADAR2共同发挥作用，强制执行允许编辑在剪接之前的事件顺序，并且它们进一步表明CTD作为两个相互依赖的pre-mRNA加工事件的协调者的新作用。
The C-terminal domain (CTD) of the large subunit of RNA polymerase II (Pol II) influences many steps in the synthesis of an mRNA and helps control the final destiny of the mature transcript. ADAR2 edits RNA by converting adenosine to inosine within double-stranded or structured RNA. Site-selective A-to-I editing often occurs at sites near exon/intron borders, where it depends on intronic sequences for substrate recognition. It is therefore essential that editing precedes splicing. We have investigated whether there is coordination between ADAR2 editing and splicing of the GluR-B pre-mRNA. We show that the CTD is required for efficient editing at the R/G site one base upstream of a 5'-splice site. The results suggest that the CTD enhances editing at the R/G site by preventing premature splicing that would remove the intronic recognition sites for ADAR2. Editing at the GluR-B Q/R site, 24 bases upstream of the intron 11 5'-splice site, stimulates splicing at this intron. Furthermore, unlike previously studied introns, the CTD actually inhibits excision of intron 11, which includes the complementary recognition sequences for the Q/R editing site. In summary, these results show that the CTD and ADAR2 function together to enforce the order of events that allows editing to precede splicing, and they furthermore suggest a new role for the CTD as a coordinator of two interdependent pre-mRNA processing events.