Intergenic RNA mainly derives from nascent transcripts of known genes.
Intergenic RNA mainly derives from nascent transcripts of known genes.
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DOI：
10.1186/s13059-021-02350-x
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发表时间：
2021-05-05
期刊：
影响因子：
12.3
通讯作者：
Luscombe NM
中科院分区：
文献类型：
--
作者：
Agostini F;Zagalak J;Attig J;Ule J;Luscombe NM
真核生物基因组进行普遍的转录，导致许多类型的稳定和不稳定的RNA的生产。转录不限于具有注释基因特征的区域，而是包括几乎任何基因组背景。目前，大多数源自人类基因组中基因间区域的RNA的来源和功能仍不清楚。我们假设，许多基因间RNA可以归因于尚未注释的基因的存在或已知基因的“模糊”转录，超出了注释的边界。为了阐明这两个来源的贡献，我们在5个人类细胞系和多个细胞区室中组装了超过25亿个公开可用的RNA-seq读数的数据集，以注释人类基因组中的转录单位。约80%的转录本来自未注释的基因间区域，可归因于现有基因的模糊转录;其余的转录本主要来自推定的长非编码RNA位点，很少剪接。我们使用独立的测量方法验证这些基因间RNA的转录活性，包括转录起始位点、染色质签名和RNA聚合酶II在各种磷酸化状态下的基因组占位。我们还分析了核定位和基因间转录物对核酸酶的敏感性，以说明它们往往被XRN 2或外泌体迅速降解。我们提供了一个精心策划的基因间RNA图谱，该图谱基于染色质特征、核RNA定位和降解途径的综合分析，区分了来自独立转录单位的注释良好的基因的替代加工。
Eukaryotic genomes undergo pervasive transcription, leading to the production of many types of stable and unstable RNAs. Transcription is not restricted to regions with annotated gene features but includes almost any genomic context. Currently, the source and function of most RNAs originating from intergenic regions in the human genome remain unclear. We hypothesize that many intergenic RNAs can be ascribed to the presence of as-yet unannotated genes or the “fuzzy” transcription of known genes that extends beyond the annotated boundaries. To elucidate the contributions of these two sources, we assemble a dataset of more than 2.5 billion publicly available RNA-seq reads across 5 human cell lines and multiple cellular compartments to annotate transcriptional units in the human genome. About 80% of transcripts from unannotated intergenic regions can be attributed to the fuzzy transcription of existing genes; the remaining transcripts originate mainly from putative long non-coding RNA loci that are rarely spliced. We validate the transcriptional activity of these intergenic RNAs using independent measurements, including transcriptional start sites, chromatin signatures, and genomic occupancies of RNA polymerase II in various phosphorylation states. We also analyze the nuclear localization and sensitivities of intergenic transcripts to nucleases to illustrate that they tend to be rapidly degraded either on-chromatin by XRN2 or off-chromatin by the exosome. We provide a curated atlas of intergenic RNAs that distinguishes between alternative processing of well-annotated genes from independent transcriptional units based on the combined analysis of chromatin signatures, nuclear RNA localization, and degradation pathways.
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影响因子：
13.8
作者：
Gates LA;Foulds CE;O'Malley BW
通讯作者：
O'Malley BW
影响因子：
64.5
作者：
Attig J;Agostini F;Gooding C;Chakrabarti AM;Singh A;Haberman N;Zagalak JA;Emmett W;Smith CWJ;Luscombe NM;Ule J
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Ule J
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10.5
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Eaton JD;Davidson L;Bauer DLV;Natsume T;Kanemaki MT;West S
通讯作者：
West S
影响因子：
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Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
5.8
作者：
Akalin, Altuna;Franke, Vedran;Schuebeler, Dirk
通讯作者：
Schuebeler, Dirk