Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast.
Widespread exon skipping triggers degradation by nuclear RNA surveillance in fission yeast.
复制标题
DOI：
10.1101/gr.185371.114
复制
发表时间：
2015-06
期刊：
影响因子：
7
通讯作者：
Bähler J
中科院分区：
文献类型：
--
作者：
Bitton DA;Atkinson SR;Rallis C;Smith GC;Ellis DA;Chen YY;Malecki M;Codlin S;Lemay JF;Cotobal C;Bachand F;Marguerat S;Mata J;Bähler J
外显子跳跃被认为是真核细胞扩增其转录组和蛋白质组库，产生具有不同细胞功能的不同剪接变体的主要机制。在这里，我们分析了来自裂殖酵母（裂殖酵母）中116个转录组的RNA-seq数据，涵盖了多种生理条件以及转录和RNA加工突变体。我们应用蛮力算法检测所有可能的外显子跳跃事件，这是普遍的，但罕见的正常剪接事件相比。外显子跳跃事件在缺乏核外泌体或5′-3′外切核酸酶Dhp 1的细胞中增加，并且在减数分裂分化的晚期，当核外泌体转录物减少时也增加。普遍的外显子跳跃转录是随机的，在特定的生理条件下不会增加，并且大多数情况下每个细胞的拷贝数小于一个，即使在没有核RNA监视的情况下和在减数分裂后期。因此，这些外显子跳跃转录不太可能是功能性的，可能反映了通过核RNA监视主动去除的剪接错误。野生型和核外切酶突变型的外显子跳跃平均剪接率分别为0.24%和1.75%。我们还检测到约250个来自单个或多个外显子的环状RNA。这些环状RNA是罕见的和随机的，虽然有一些在静止期和剪接突变体中变得稳定。使用穷举搜索算法，我们还发现了数千个以前未知的剪接位点，表明普遍的剪接，但大多数这些剪接变异体是神秘的，并在核降解突变体中增加。这项研究强调了广泛但低频率的选择性或异常剪接事件，这些事件是核RNA监测的目标。
Exon skipping is considered a principal mechanism by which eukaryotic cells expand their transcriptome and proteome repertoires, creating different splice variants with distinct cellular functions. Here we analyze RNA-seq data from 116 transcriptomes in fission yeast (Schizosaccharomyces pombe), covering multiple physiological conditions as well as transcriptional and RNA processing mutants. We applied brute-force algorithms to detect all possible exon-skipping events, which were widespread but rare compared to normal splicing events. Exon-skipping events increased in cells deficient for the nuclear exosome or the 5′-3′ exonuclease Dhp1, and also at late stages of meiotic differentiation when nuclear-exosome transcripts decreased. The pervasive exon-skipping transcripts were stochastic, did not increase in specific physiological conditions, and were mostly present at less than one copy per cell, even in the absence of nuclear RNA surveillance and during late meiosis. These exon-skipping transcripts are therefore unlikely to be functional and may reflect splicing errors that are actively removed by nuclear RNA surveillance. The average splicing rate by exon skipping was ∼0.24% in wild type and ∼1.75% in nuclear exonuclease mutants. We also detected approximately 250 circular RNAs derived from single or multiple exons. These circular RNAs were rare and stochastic, although a few became stabilized during quiescence and in splicing mutants. Using an exhaustive search algorithm, we also uncovered thousands of previously unknown splice sites, indicating pervasive splicing; yet most of these splicing variants were cryptic and increased in nuclear degradation mutants. This study highlights widespread but low frequency alternative or aberrant splicing events that are targeted by nuclear RNA surveillance.
登录
查看更多内容
影响因子：
64.5
作者：
Cooper TA;Wan L;Dreyfuss G
通讯作者：
Dreyfuss G
影响因子：
12.3
作者：
Gonzàlez-Porta M;Frankish A;Rung J;Harrow J;Brazma A
通讯作者：
Brazma A
影响因子：
10.5
作者：
Boutz PL;Bhutkar A;Sharp PA
通讯作者：
Sharp PA
影响因子：
14.9
作者：
Flicek P;Amode MR;Barrell D;Beal K;Billis K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fitzgerald S;Gil L;Girón CG;Gordon L;Hourlier T;Hunt S;Johnson N;Juettemann T;Kähäri AK;Keenan S;Kulesha E;Martin FJ;Maurel T;McLaren WM;Murphy DN;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ruffier M;Sheppard D;Taylor K;Thormann A;Trevanion SJ;Vullo A;Wilder SP;Wilson M;Zadissa A;Aken BL;Birney E;Cunningham F;Harrow J;Herrero J;Hubbard TJ;Kinsella R;Muffato M;Parker A;Spudich G;Yates A;Zerbino DR;Searle SM
通讯作者：
Searle SM
影响因子：
7
作者：
Braunschweig U;Barbosa-Morais NL;Pan Q;Nachman EN;Alipanahi B;Gonatopoulos-Pournatzis T;Frey B;Irimia M;Blencowe BJ
通讯作者：
Blencowe BJ