武汉植物园在PNAS报道长链非编码RNA调控基因转录研究新进展
中国科学院武汉植物园与英国John Innes Centre 合作,通过突变体的筛选,发现CDKC;2虽为正向转录延伸因子P-TEFb复合体的激酶亚基,却对拟南芥开花时间重要调控基因FLC的转录表现为抑制作用。相关文章发表于2014年5月5日的《PNAS》杂志上。
CDKC;2调控FLC转录建议模型
长链非编码rna(long noncoding RNA, lncRNA)一般指长度大于200个核苷酸的非编码RNA,目前已在多种生物中发现了大量lncRNA,然而只有少数lncRNA的精细作用机理被阐明。
中国科学院武汉植物园汪志伟博士在植物种群遗传学科组王艇研究员支持和中国科学院留学基金资助下,与英国John Innes Centre 的Caroline Dean教授合作,通过突变体的筛选,发现CDKC;2虽为正向转录延伸因子P-TEFb复合体的激酶亚基,却对拟南芥开花时间重要调控基因FLC的转录表现为抑制作用。
前期研究在FLC位点发现了一组名为COOLAIR的反义转录本。受此启发,本研究阐明CDKC;2直接促进COOLAIR的转录。
进一步解析表明不含COOLAIR启动子的FLC转录不受CDKC;2的影响。从而揭示出cdkc;2突变下调了COOLAIR的转录,进而扰乱了COOLAIR介导的抑制机制,最终导致FLC上调表达。这种P-TEFb通过调节反义lncRNA的转录来间接微调功能基因表达的机制可能在真核生物中具有普遍意义。
5月5日,相关研究结果在线发表于PNAS。
原文摘要:
Zhi-Wei Wang, Zhe Wu, Oleg Raitskin, Qianwen Sun and Caroline Dean
The functional significance of noncoding transcripts is currently a major question in biology. We have been studying the function of a set of antisense transcripts called COOLAIR that encompass the whole transcription unit of the Arabidopsis floral repressor FLOWERING LOCUS C (FLC). Alternative polyadenylation of COOLAIR transcripts correlates with different FLC sense expression states. Suppressor mutagenesis aimed at understanding the importance of this sense–antisense transcriptional circuitry has identified a role for Arabidopsis cyclin-dependent kinase C (CDKC;2) in FLC repression. CDKC;2 functions in an Arabidopsis positive transcription elongation factor b (P-TEFb) complex and influences global RNA polymerase II (Pol II) Ser2 phosphorylation levels. CDKC;2 activity directly promotes COOLAIR transcription but does not affect an FLC transgene missing the COOLAIR promoter. In the endogenous gene context, however, the reduction of COOLAIR transcription by cdkc;2 disrupts a COOLAIR-mediated repression mechanism that increases FLC expression. This disruption then feeds back to indirectly increase COOLAIRexpression. This tight interconnection between sense and antisense transcription, together with differential promoter sensitivity to P-TEFb, is central to quantitative regulation of this important floral repressor gene.
作者:中科院