Milligan Michael J, Lipovich Leonard
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine , Detroit, MI, USA.
Front Genet. 2015 Feb 4;5:476. doi: 10.3389/fgene.2014.00476. eCollection 2014.
In the more than one decade since the completion of the Human Genome Project, the prevalence of non-protein-coding functional elements in the human genome has emerged as a key revelation in post-genomic biology. Highlighted by the ENCODE (Encyclopedia of DNA Elements) and FANTOM (Functional Annotation of Mammals) consortia, these elements include tens of thousands of pseudogenes, as well as comparably numerous long non-coding RNA (lncRNA) genes. Pseudogene transcription and function remain insufficiently understood. However, the field is of great importance for human disease due to the high sequence similarity between pseudogenes and their parental protein-coding genes, which generates the potential for sequence-specific regulation. Recent case studies have established essential and coordinated roles of both pseudogenes and lncRNAs in development and disease in metazoan systems, including functional impacts of lncRNA transcription at pseudogene loci on the regulation of the pseudogenes' parental genes. This review synthesizes the nascent evidence for regulatory modalities jointly exerted by lncRNAs and pseudogenes in human disease, and for recent evolutionary origins of these systems.
自人类基因组计划完成后的十多年里，人类基因组中非蛋白质编码功能元件的普遍存在已成为后基因组生物学中的一项关键发现。以ENCODE（DNA元件百科全书）和FANTOM（哺乳动物功能注释）联盟为突出代表，这些元件包括数以万计的假基因，以及数量相当的长链非编码RNA（lncRNA）基因。假基因的转录和功能仍未得到充分了解。然而，由于假基因与其亲本蛋白质编码基因之间的高度序列相似性，该领域对人类疾病具有重要意义，这就产生了序列特异性调控的可能性。最近的案例研究已经确定了假基因和lncRNA在后生动物系统的发育和疾病中的重要且协同的作用，包括lncRNA在假基因位点的转录对假基因亲本基因调控的功能影响。本综述综合了lncRNA和假基因在人类疾病中共同发挥的调控方式的新证据，以及这些系统最近的进化起源。
