Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K.
Inter-species association mapping links splice site evolution to METTL16 and SNRNP27K.
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种间关联映射链接链接站点的演变与mettl16和snrnp27k。
DOI：
10.7554/elife.91997
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发表时间：
2023-10-03
期刊：
影响因子：
7.7
通讯作者：
Simpson GG
中科院分区：
文献类型：
--
作者：
Parker MT;Fica SM;Barton GJ;Simpson GG
真核基因被内含子中断，内含子通过剪接从转录的RNA中去除。剪接复杂性的模式在物种之间存在差异，但目前还不清楚这些差异是如何产生的。我们使用了种间关联映射与亚门真菌种相关的剪接信号表型与剪接因子的存在或不存在。在这里，我们表明，5'剪接位点序列偏好的变化与U6 snRNA N6-甲基腺苷甲基转移酶胃L16和剪接因子SNRNP 27 K的存在相关。5'剪接位点序列的最大变异发生在+4位，并涉及腺苷和尿苷之间的偏好转换。缺失胸腺L16和SNRNP 27 K直系同源物或单个SNRNP 27 K甲硫氨酸残基与+4 U的偏好相关。这些发现与对在胃L16或SNRNP 27 K直向同源物中有缺陷的突变体和源自剪接体结构的模型的剪接分析一致，表明种间关联作图是分子研究的有力正交方法。我们确定了两个主要类别的5'剪接位点的发生在物种之间的变化，由不同的相互作用潜力与U 5和U6 snRNAs，与内含子数相关的定义。我们的结论是U6 snRNA的5'剪接位点选择协同过程的变化与剪接信号表型的进化变化有关。
Eukaryotic genes are interrupted by introns that are removed from transcribed RNAs by splicing. Patterns of splicing complexity differ between species, but it is unclear how these differences arise. We used inter-species association mapping with Saccharomycotina species to correlate splicing signal phenotypes with the presence or absence of splicing factors. Here, we show that variation in 5’ splice site sequence preferences correlate with the presence of the U6 snRNA N6-methyladenosine methyltransferase METTL16 and the splicing factor SNRNP27K. The greatest variation in 5’ splice site sequence occurred at the +4 position and involved a preference switch between adenosine and uridine. Loss of METTL16 and SNRNP27K orthologs, or a single SNRNP27K methionine residue, was associated with a preference for +4 U. These findings are consistent with splicing analyses of mutants defective in either METTL16 or SNRNP27K orthologs and models derived from spliceosome structures, demonstrating that inter-species association mapping is a powerful orthogonal approach to molecular studies. We identified variation between species in the occurrence of two major classes of 5’ splice sites, defined by distinct interaction potentials with U5 and U6 snRNAs, that correlates with intron number. We conclude that variation in concerted processes of 5’ splice site selection by U6 snRNA is associated with evolutionary changes in splicing signal phenotypes.
DOI：
10.1126/science.1194554
发表时间：
2010-11-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mitrovich QM;Tuch BB;De La Vega FM;Guthrie C;Johnson AD
通讯作者：
Johnson AD