mRNA splicing and autocatalytic introns: Distant cousins or the products of chemical determinism?
mRNA splicing and autocatalytic introns: Distant cousins or the products of chemical determinism?
复制标题
mRNA 剪接和自催化内含子：远亲还是化学决定论的产物？
DOI：
10.1016/0092-8674(93)90654-9
复制
发表时间：
1993
期刊：
影响因子：
64.5
通讯作者：
A. Weiner
中科院分区：
文献类型：
--
作者：
A. Weiner
核信使RNA（mRNA）剪接和II组内含子的自催化切除之间的明显机制相似性（图1）很早就导致了mRNA剪接可能是II组自我剪接的远亲进化关系的假设（Sharp，1985; Cech，1986）。这一假设的两个直接含义-mRNA剪接可能是一个基本的RNA催化反应，以及五个剪接体小核RNA（U1，U2，U4，U 5和U6 snRNA）与mRNA前体一起可能在某种深层意义上代表第II组内含子的片段-具有直接的吸引力，但进一步的证据积累缓慢。在过去的两年里，这一领域的突破来得又快又密，最终取得了一系列惊人的进展（Fabrizio和Abelson，1990年; Madhani等人，1990;纽曼和诺曼，1992;赖希等人，一九九二年; Sawa and Shimura，1992; Steitz，1992; Wassarman and Steitz，1992），其中两个出现在最近一期的Cell上（Madhani and古特里，1992; McPheeters and Abelson，1992）。这些进步带来了越来越多的RNA爱好者（591名研究人员参加了1992年的RNA加工会议！）非常接近mRNA剪接的催化中心好消息是，RNA在催化mRNA剪接中的直接作用的证据越来越强。具有讽刺意味的是，这种新的知识可能不一定支持与第二组内含子的进化关系。为什么认为U2和U6具有催化作用从酵母到人类，五种剪接体snRNA的二级结构都很保守，U1、U4和U 5中的一级序列片段也是如此，但是沿着U6全长（约100 nt）和U2 snRNA 5 '端（约90 nt）的一级序列沿着的保守性简直是非同寻常的（古特里，1991）。这一点本身就有利于U6 snRNA在mRNA剪接中的催化作用，但也有许多其他提示：在剪接的第一个催化步骤发生之前，U6和U4之间的大量碱基配对必须解旋，这表明U4可能阿萨U6的阻遏物发挥作用（综述于Madhani et al.，1990年）;在两个不变的U6序列基序ACAGAGA和AGC内的突变可以特异性地阻断两者在体内剪接的第一或第二步骤（Madhani等，1990）和体外（Fabrizio和Abelson，1990）; U6可以光化学交联到5 '剪接位点附近（Sawa和Abelson，1992; Sawa和Shimura，1992; Wassarman和Steitz，1992）;和U6 snRNA基因在几种酵母中含有典型的mRNA内含子，这些内含子可能是通过异常的反向剪接，随后是逆转录和染色体畸变而产生的。整合（在古特里，1991年审查）。
The obvious mechanistic similarities between nuclear messenger RNA (mRNA) splicing and autocatalytic excision of group II introns (Figure 1) led very early to the hypothesis that mRNA splicing might be a distant evolutionary relative of group II self-splicing (Sharp, 1985; Cech, 1986). The two immediate implications of this hypothesis-that mRNA splicing might be a fundamentally RNA-catalyzed reaction and that the five spliceosomal small nuclear RNAs (Ul, U2, U4, U5, and U6 snRNAs) together with the mRNA precursor might in some deep sense represent fragments of a group II intron-had immediate appeal, but further evidence was slow to accumulate. Over the past two years, breakthroughs in this area have come thick and fast, culminating with a series of spectacular advances (Fabrizio and Abelson, 1990; Madhani et al., 1990; Newman and Norman, 1992; Reich et al., 1992; Sawa and Shimura, 1992; Steitz, 1992; Wassarman and Steitz, 1992), two of which appeared in a recent issue of Cell (Madhani and Guthrie, 1992; McPheeters and Abelson, 1992). These advances have brought the ever larger community of RNA aficionados (591 investigators attended the 1992 RNA Processing Meeting!) tantalizingly close to the catalytic center of mRNA splicing. The good news is that evidence for a direct role of RNA in catalysis of mRNA splicing is getting stronger all the time. Ironically, this new knowledge may not necessarily support an evolutionary relationship with group II introns. Why U2 and U6 Are Thought to Be Catalytic The secondary structures of the five spliceosomal snRNAs are well conserved from yeast to humans, as are patches of primary sequence in Ul, U4, and U5, but conservation of primary sequence along the entire length of U6 (about 100 nt) and at the 5’end of U2 snRNA (for about 90 nt) is simply extraordinary (Guthrie, 1991). This alone would favor a catalytic role for U6 snRNA in mRNA splicing, but there are many other hints as well: extensive base pairing between U6 and U4 must be unwound before the first catalytic step of splicing can take place, suggesting that U4mayfunction asa repressor of U6 (reviewed in Madhani et al., 1990); mutations within two invariant U6 sequence motifs, ACAGAGA and AGC, can specifically block the first or second steps of splicing both in vivo (Madhani et al., 1990) and in vitro (Fabrizio and Abelson, 1990); U6 can be photochemically cross-linked to the vicinity of the 5’splice site (Sawa and Abelson, 1992; Sawa and Shimura, 1992; Wassarman and Steitz, 1992); and U6 snRNA genes in several yeasts contain typical mRNA introns that could have arisen by aberrant reverse splicing followed by reverse transcription and chromosomal integration (reviewed in Guthrie, 1991).
登录
查看更多内容
通过 NMR 和能量最小化得出含有凸出鸟苷的寡核苷酸的结构模型。
影响因子：
2.9
作者：
Woodson,SA;Crothers,DM
通讯作者：
Crothers,DM
四膜虫前体 RNA 中的轴向结合位点。
影响因子：
5.6
作者：
Yarus,M;Illangesekare,M;Christian,E
通讯作者：
Christian,E
删除多个子结构的第二组内含子保留了自剪接活性。
影响因子：
5.3
作者：
Koch,JL;Boulanger,SC;Dib-Hajj,SD;Hebbar,SK;Perlman,PS
通讯作者：
Perlman,PS
影响因子：
56.9
作者：
MOORE, MJ;SHARP, PA
通讯作者：
SHARP, PA
影响因子：
56.9
作者：
WASSARMAN, DA;STEITZ, JA
通讯作者：
STEITZ, JA