Long noncoding RNAs are rarely translated in two human cell lines.
Long noncoding RNAs are rarely translated in two human cell lines.
复制标题
DOI：
10.1101/gr.134767.111
复制
发表时间：
2012-09
期刊：
影响因子：
7
通讯作者：
Lipovich L
中科院分区：
文献类型：
--
作者：
Bánfai B;Jia H;Khatun J;Wood E;Risk B;Gundling WE Jr;Kundaje A;Gunawardena HP;Yu Y;Xie L;Krajewski K;Strahl BD;Chen X;Bickel P;Giddings MC;Brown JB;Lipovich L
DNA元件百科全书（ENCODE）项目的数据显示，有超过9640个人类基因组位点被归类为长链非编码RNA（lncRNAs），然而只有约100个得到了深入的特性分析以确定它们在细胞中的作用。为了测量这些RNA的蛋白质编码输出，我们联合分析了ENCODE项目中产生的两个近期数据集：将表达的肽段映射到其编码基因组位点的串联质谱（MS/MS）数据，以及ENCODE在细胞系K562和GM12878的长polyA⁺和polyA⁻组分中生成的RNA - seq数据。我们使用机器学习算法RuleFit3将肽段数据与RNA表达数据进行回归分析。令人惊讶的是，预测翻译的最重要协变量是两种细胞系中的细胞质polyA⁻组分。lncRNAs产生可检测肽段的可能性比类似的mRNAs低约13倍，这表明在这两种ENCODE细胞系中，约92%的GENCODE v7 lncRNAs不被翻译。将9640个lncRNA位点与79333个肽段相交，得到了85个独特的肽段，它们与69个lncRNAs匹配。大多数情况是由于一个编码转录本被错误注释为lncRNA。两个例外是一个未加工的假基因和一个真正的lncRNA基因，它们的开放阅读框（ORFs）都因上游的终止密码子而受损。所有可能可翻译的lncRNA ORFs都只有一个肽段匹配，这表明蛋白质丰度低和/或肽段匹配为假阳性。我们得出结论，除了极少数例外，核糖体能够区分编码转录本和非编码转录本，因此，异位翻译和隐蔽mRNA在人类lncRNA组中是罕见的。
Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human genome loci classified as long noncoding RNAs (lncRNAs), yet only ∼100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these RNAs, we jointly analyzed two recent data sets produced in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in long polyA+ and polyA− fractions in the cell lines K562 and GM12878. We used the machine-learning algorithm RuleFit3 to regress the peptide data against RNA expression data. The most important covariate for predicting translation was, surprisingly, the Cytosol polyA− fraction in both cell lines. LncRNAs are ∼13-fold less likely to produce detectable peptides than similar mRNAs, indicating that ∼92% of GENCODE v7 lncRNAs are not translated in these two ENCODE cell lines. Intersecting 9640 lncRNA loci with 79,333 peptides yielded 85 unique peptides matching 69 lncRNAs. Most cases were due to a coding transcript misannotated as lncRNA. Two exceptions were an unprocessed pseudogene and a bona fide lncRNA gene, both with open reading frames (ORFs) compromised by upstream stop codons. All potentially translatable lncRNA ORFs had only a single peptide match, indicating low protein abundance and/or false-positive peptide matches. We conclude that with very few exceptions, ribosomes are able to distinguish coding from noncoding transcripts and, hence, that ectopic translation and cryptic mRNAs are rare in the human lncRNAome.
登录
查看更多内容
影响因子：
3.1
作者：
Hube, Florent;Guo, Jimin;Leygue, Etienne
通讯作者：
Leygue, Etienne
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
64.5
作者：
Huarte M;Guttman M;Feldser D;Garber M;Koziol MJ;Kenzelmann-Broz D;Khalil AM;Zuk O;Amit I;Rabani M;Attardi LD;Regev A;Lander ES;Jacks T;Rinn JL
通讯作者：
Rinn JL
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
7
作者：
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