Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing.
Heteromeric RNP Assembly at LINEs Controls Lineage-Specific RNA Processing.
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DOI：
10.1016/j.cell.2018.07.001
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发表时间：
2018-08-23
期刊：
影响因子：
64.5
通讯作者：
Ule J
中科院分区：
文献类型：
--
作者：
Attig J;Agostini F;Gooding C;Chakrabarti AM;Singh A;Haberman N;Zagalak JA;Emmett W;Smith CWJ;Luscombe NM;Ule J
长的哺乳动物内含子使得RNA加工机器准确识别外显子具有挑战性。我们发现LINE衍生序列（LINE）通过招募数十个RNA结合蛋白（RBP）到内含子来促进这种选择。这包括MATR 3，其促进PTBP 1与LINE内的多价结合位点的结合。两种RBP都抑制LINE内和周围的剪接和3′端加工。值得注意的是，抑制性RBP优先结合进化上年轻的LINE，其位于远离外显子。这些RBP将LINE和周围的内含子区域与RNA加工隔离。在进化分化后，LINE内RNA基序的变化导致其绝缘性逐渐丧失。因此，较老的LINE更靠近外显子，是组织特异性外显子的共同来源，并且越来越多地与增强RNA加工的RBP结合。因此，LINE是抑制性RBP组装的中心，也有助于哺乳动物中新的谱系特异性转录物的进化。年轻LINE中的多价结合位点主要募集抑制性RBP PTBP 1和MATR 3共结合并抑制年轻LINE内和周围的RNA加工来自外显子附近的LINE的1-kb排除区反映了它们的抑制作用序列驱动的RBP在旧LINE上的重塑驱动组织特异性外显子的进化LINE元件将RNA结合蛋白募集到哺乳动物内含子，影响剪接并在组织特异性外显子的进化中起关键作用。
Long mammalian introns make it challenging for the RNA processing machinery to identify exons accurately. We find that LINE-derived sequences (LINEs) contribute to this selection by recruiting dozens of RNA-binding proteins (RBPs) to introns. This includes MATR3, which promotes binding of PTBP1 to multivalent binding sites within LINEs. Both RBPs repress splicing and 3′ end processing within and around LINEs. Notably, repressive RBPs preferentially bind to evolutionarily young LINEs, which are located far from exons. These RBPs insulate the LINEs and the surrounding intronic regions from RNA processing. Upon evolutionary divergence, changes in RNA motifs within LINEs lead to gradual loss of their insulation. Hence, older LINEs are located closer to exons, are a common source of tissue-specific exons, and increasingly bind to RBPs that enhance RNA processing. Thus, LINEs are hubs for the assembly of repressive RBPs and also contribute to the evolution of new, lineage-specific transcripts in mammals. Multivalent binding sites in young LINEs mainly recruit repressive RBPs PTBP1 and MATR3 co-bind and repress RNA processing within and around young LINEs 1-kb exclusion zone of LINEs from vicinity of exons reflects their repressive effects Sequence-driven RBP remodeling on old LINEs drives evolution of tissue-specific exons LINE elements recruit RNA-binding proteins to mammalian introns, influencing splicing and playing a key role in the evolution of tissue-specific exons.
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影响因子：
4.8
作者：
Huppertz, Ina;Attig, Jan;D'Ambrogio, Andrea;Easton, Laura E.;Sibley, Christopher R.;Sugimoto, Yoichiro;Tajnik, Mojca;Koenig, Julian;Ule, Jernej
通讯作者：
Ule, Jernej
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
LINE-1 RNA剪接和对哺乳动物基因表达的影响。
影响因子：
14.9
作者：
Belancio, VP;Hedges, DJ;Deininger, P
通讯作者：
Deininger, P
影响因子：
12.3
作者：
Corvelo A;Eyras E
通讯作者：
Eyras E
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH