Wills Norma M, Atkins John F
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA.
RNA. 2006 Jul;12(7):1149-53. doi: 10.1261/rna.84406. Epub 2006 May 18.
Aberrant forms of proteins ubiquitin B and beta-amyloid precusor protein, UBB+1 and APP+1, are implicated in human neurodegenerative diseases. They have their carboxyl-terminal regions derived from an alternative reading frame. Transcription slippage has been invoked to explain the production of these proteins from abnormal mRNA. However, ribosomal frameshifting on wild-type mRNA may account for the great majority of the aberrant protein. Ribosomal frameshifting may also be involved in the progression of triplet expansion diseases such as Huntington's and spinocerebellar ataxias. In a particular spinocerebellar ataxia, SCA3, Toulouse and colleagues recently discovered -1 frameshifting in a transcript containing an expanded CAG-repeat. Antibiotics that affect mammalian ribosomes may have complex effects on frameshifting and disease progression.
泛素B和β-淀粉样前体蛋白的异常形式，即UBB +1和APP +1，与人类神经退行性疾病有关。它们的羧基末端区域来自一个替代阅读框。转录滑动被用来解释这些蛋白质从异常mRNA的产生。然而，野生型mRNA上的核糖体移码可能是绝大多数异常蛋白质的原因。核糖体移码也可能参与三联体扩增疾病的进展，如亨廷顿舞蹈症和脊髓小脑共济失调。在一种特定的脊髓小脑共济失调，即SCA3中，图卢兹及其同事最近在一个含有扩展CAG重复序列的转录本中发现了-1移码。影响哺乳动物核糖体的抗生素可能对移码和疾病进展有复杂的影响。
