Sharma Yashica, Vo Kevin, Shila Sharmin, Paul Anohita, Dahiya Vinesh, Fields Patrick E, Rumi M A Karim
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Int J Mol Sci. 2025 Jan 26;26(3):1052. doi: 10.3390/ijms26031052.
Gene expression or gene regulation studies often assume one gene expresses one mRNA. However, contrary to the conventional idea, a single gene in mammalian cells can express multiple transcript variants translated into several different proteins. The transcript variants are generated through transcription from alternative start sites and alternative post-transcriptional processing of the precursor mRNA (pre-mRNA). In addition, gene mutations and RNA editing further enhance the diversity of the transcript variants. The transcript variants can encode proteins with various domains, expanding the functional repertoire of a single gene. Some transcript variants may not encode proteins but function as non-coding RNAs and regulate gene expression. The expression level of the transcript variants may vary between cell types or within the same cells under different biological conditions. Transcript variants are characteristic of cell differentiation in a particular tissue, and the variants may play a key role in normal development and aging. Studies also reported that some transcript variants may have roles in disease pathogenesis. The biological significances urge studying the complexity of gene expression at the transcript level. This article updates the molecular basis of transcript variants in mammalian cells, including the formation mechanisms and potential roles in host biology. Gaining insight into the transcript variants will not only identify novel mechanisms of gene regulation but also unravel the role of the variants in health and disease.
基因表达或基因调控研究通常假定一个基因表达一种信使核糖核酸(mRNA)。然而,与传统观念相反,哺乳动物细胞中的单个基因可以表达多种转录变体,这些变体可被翻译为几种不同的蛋白质。转录变体是通过从前体mRNA(pre-mRNA)的可变起始位点转录以及可变的转录后加工产生的。此外,基因突变和RNA编辑进一步增加了转录变体的多样性。转录变体可以编码具有各种结构域的蛋白质,从而扩展了单个基因的功能库。一些转录变体可能不编码蛋白质,而是作为非编码RNA发挥作用并调控基因表达。转录变体的表达水平在不同细胞类型之间或在不同生物学条件下的同一细胞内可能有所不同。转录变体是特定组织中细胞分化的特征,这些变体可能在正常发育和衰老过程中起关键作用。研究还报告称,一些转录变体可能在疾病发病机制中发挥作用。这些生物学意义促使人们在转录水平上研究基因表达的复杂性。本文更新了哺乳动物细胞中转录变体的分子基础,包括其形成机制以及在宿主生物学中的潜在作用。深入了解转录变体不仅将识别基因调控的新机制,还将揭示这些变体在健康和疾病中的作用。