Do long noncoding RNAs (lncRNAs) contribute little or substantively to human biology? To address how lncRNA loci and their transcripts, structures, interactions, and functions contribute to human traits and disease, we adopt a genome-wide perspective. We intend to provoke alternative interpretation of questionable evidence and thorough inquiry into unsubstantiated claims. We discuss pitfalls of lncRNA experimental and computational methods as well as opposing interpretations of their results. The majority of evidence, we argue, indicates that most lncRNA transcript models reflect transcriptional noise or provide minor regulatory roles, leaving relatively few human lncRNAs that contribute centrally to human development, physiology, or behavior. These important few tend to be spliced and better conserved but lack a simple syntax relating sequence to structure and mechanism, and so resist simple categorization. This genome-wide view should help investigators prioritize individual lncRNAs based on their likely contribution to human biology.

中文翻译：

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人类长非编码 RNA 的全基因组分析：一项颇具争议性的综述

长链非编码 RNA (lncRNA) 对人类生物学贡献很小还是有实质性贡献？为了解决 lncRNA 位点及其转录本、结构、相互作用和功能如何影响人类特征和疾病，我们采用全基因组视角。我们打算对有问题的证据提出不同的解释，并对未经证实的主张进行彻底调查。我们讨论了 lncRNA 实验和计算方法的陷阱以及对其结果的相反解释。我们认为，大多数证据表明，大多数 lncRNA 转录模型反映了转录噪音或提供了次要的调节作用，使得对人类发育、生理或行为做出主要贡献的人类 lncRNA 相对较少。这些重要的少数往往被拼接并更好地保存，但缺乏将序列与结构和机制相关的简单语法，因此抵制简单的分类。这种全基因组视图应该有助于研究人员根据单个 lncRNA 对人类生物学的可能贡献来优先考虑它们。