P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation
P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation
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DOI：
10.1016/j.molcel.2005.11.024
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发表时间：
2006-01-20
期刊：
影响因子：
16
通讯作者：
Handa, H
中科院分区：
文献类型：
--
作者：
Yamada, T;Yamaguchi, Y;Handa, H
人DSIF是由hSpt4和hSpt5组成的异源二聚体，在RNA聚合酶II(RNA Pol II)的转录延伸中起相反的作用。在这里，我们描述了hSpt5 C-末端区域(CTR)上一个进化保守的重复七肽基序(共识=G-S-R/Q-T-P)，与RNAPolII的C-末端结构域一样，它被P-TEFb高度磷酸化。CTR重复序列中的Thr-4残基是重要的功能磷酸化位点。在体外，Thr-4的磷酸化对DSIF的伸长激活活性是关键的，但对其伸长抑制活性并不关键。在体内，Thr-4的磷酸化对于表皮生长因子(EGF)诱导的c-fos的转录和RNA Pol沿着基因的有效进展是至关重要的。我们认为这种磷酸化是将dsif从抑制子转换为激活子的开关。我们提出了‘’迷你CTD‘’假说，其中磷酸化的CTR被认为以类似于磷酸化的CTD的方式发挥作用，作为活性延长复合体的额外代码。
Human DSIF, a heterodimer composed of hSpt4 and hSpt5, plays opposing roles in transcription elongation by RNA polymerase II (RNA Pol II). Here, we describe an evolutionarily conserved repetitive heptapeptide motif (consensus = G-S-R/Q-T-P) in the C-terminal region (CTR) of hSpt5, which, like the C-terminal domain (CTD) of RNA Pol II, is highly phosphorylated by P-TEFb. Thr-4 residues of the CTR repeats are functionally important phosphorylation sites. In vitro, Thr-4 phosphorylation is critical for the elongation activation activity of DSIF, but not to its elongation repression activity. In vivo, Thr-4 phosphorylation is critical for epidermal growth factor (EGF)-inducible transcription of c-fos and for efficient progression of RNA Pol If along the gene. We consider this phosphorylation to be a switch that converts DSIF from a repressor to an activator. We propose the '' mini-CTD '' hypothesis, in which phosphorylated CTR is thought to function in a manner analogous to phosphorylated CTD, serving as an additional code for active elongation complexes.