Mattick John S, Makunin Igor V
ARC Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R121-32. doi: 10.1093/hmg/ddi101.
Mammalian cells harbor numerous small non-protein-coding RNAs, including small nucleolar RNAs (snoRNAs), microRNAs (miRNAs), short interfering RNAs (siRNAs) and small double-stranded RNAs, which regulate gene expression at many levels including chromatin architecture, RNA editing, RNA stability, translation, and quite possibly transcription and splicing. These RNAs are processed by multistep pathways from the introns and exons of longer primary transcripts, including protein-coding transcripts. Most show distinctive temporal- and tissue-specific expression patterns in different tissues, including embryonal stem cells and the brain, and some are imprinted. Small RNAs control a wide range of developmental and physiological pathways in animals, including hematopoietic differentiation, adipocyte differentiation and insulin secretion in mammals, and have been shown to be perturbed in cancer and other diseases. The extent of transcription of non-coding sequences and the abundance of small RNAs suggests the existence of an extensive regulatory network on the basis of RNA signaling which may underpin the development and much of the phenotypic variation in mammals and other complex organisms and which may have different genetic signatures from sequences encoding proteins.
哺乳动物细胞含有众多小的非蛋白质编码RNA，包括小核仁RNA（snoRNA）、微小RNA（miRNA）、小干扰RNA（siRNA）和小双链RNA，它们在包括染色质结构、RNA编辑、RNA稳定性、翻译以及很可能还有转录和剪接等多个层面调控基因表达。这些RNA由较长初级转录本（包括蛋白质编码转录本）的内含子和外显子通过多步途径加工而成。大多数在不同组织（包括胚胎干细胞和大脑）中呈现出独特的时空特异性表达模式，有些还表现为印记基因。小RNA控制着动物体内广泛的发育和生理途径，包括哺乳动物的造血分化、脂肪细胞分化和胰岛素分泌，并且已被证明在癌症和其他疾病中受到干扰。非编码序列的转录程度和小RNA的丰度表明存在一个基于RNA信号传导的广泛调控网络，该网络可能是哺乳动物和其他复杂生物体发育及许多表型变异的基础，并且可能具有与蛋白质编码序列不同的遗传特征。
