Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
Thousands of novel translated open reading frames in humans inferred by ribosome footprint profiling
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DOI：
10.7554/elife.13328
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发表时间：
2016-05-27
期刊：
影响因子：
7.7
通讯作者：
Ptitchard, Jonathan K.
中科院分区：
文献类型：
--
作者：
Raj, Anil;Wang, Sidney H.;Ptitchard, Jonathan K.
蛋白质编码区的精确注释对于理解遗传信息如何转化为功能至关重要。我们描述了riboHMM，一种新的方法，使用核糖体足迹数据来准确地推断翻译序列。将riboHMM应用于人淋巴母细胞系，我们鉴定了7273个新的编码序列，包括2442个翻译的上游开放阅读框。我们观察到丰富的足迹推断的起始位点后，药物诱导的逮捕翻译起始，验证了许多新的编码序列。新的蛋白质在推断的阅读框架中表现出显着的选择性约束，表明许多是功能性的。此外，大约40%的双顺反子转录本的两个编码序列的翻译水平呈负相关，这表明这些新区域可能具有潜在的调控作用。尽管已知质谱法在检测低水平表达的蛋白质方面存在局限性，但我们估计验证率为14%。我们的工作大大扩展了人类已知的编码区域。
Accurate annotation of protein coding regions is essential for understanding how genetic information is translated into function. We describe riboHMM, a new method that uses ribosome footprint data to accurately infer translated sequences. Applying riboHMM to human lymphoblastoid cell lines, we identified 7273 novel coding sequences, including 2442 translated upstream open reading frames. We observed an enrichment of footprints at inferred initiation sites after drug-induced arrest of translation initiation, validating many of the novel coding sequences. The novel proteins exhibit significant selective constraint in the inferred reading frames, suggesting that many are functional. Moreover, similar to 40% of bicistronic transcripts showed negative correlation in the translation levels of their two coding sequences, suggesting a potential regulatory role for these novel regions. Despite known limitations of mass spectrometry to detect protein expressed at low level, we estimated a 14% validation rate. Our work significantly expands the set of known coding regions in humans.