BioSciences Institute, University College Cork, Cork, Ireland.
J Mol Biol. 2010 Mar 26;397(2):448-56. doi: 10.1016/j.jmb.2010.01.044. Epub 2010 Jan 28.
Programmed ribosomal frameshifting allows the synthesis of alternative, N-terminally coincident, C-terminally distinct proteins from the same RNA. Many viruses utilize frameshifting to optimize the coding potential of compact genomes, to circumvent the host cell's canonical rule of one functional protein per mRNA, or to express alternative proteins in a fixed ratio. Programmed frameshifting is also used in the decoding of a small number of cellular genes. Recently, specific ribosomal -1 frameshifting was discovered at a conserved U_UUU_UUA motif within the sequence encoding the alphavirus 6K protein. In this case, frameshifting results in the synthesis of an additional protein, termed TF (TransFrame). This new case of frameshifting is unusual in that the -1 frame ORF is very short and completely embedded within the sequence encoding the overlapping polyprotein. The present work shows that there is remarkable diversity in the 3' sequences that are functionally important for efficient frameshifting at the U_UUU_UUA motif. While many alphavirus species utilize a 3' RNA structure such as a hairpin or pseudoknot, some species (such as Semliki Forest virus) apparently lack any intra-mRNA stimulatory structure, yet just 20 nt 3'-adjacent to the shift site stimulates up to 10% frameshifting. The analysis, both experimental and bioinformatic, significantly expands the known repertoire of -1 frameshifting stimulators in mammalian and insect systems.
程序性核糖体移码允许从同一条 RNA 合成替代的、N 端一致但 C 端不同的蛋白质。许多病毒利用移码来优化紧凑基因组的编码潜力，以规避宿主细胞一条 mRNA 对应一个功能蛋白的规范规则，或在固定比例下表达替代蛋白。程序性移码也用于少数细胞基因的解码。最近，在编码甲型病毒 6K 蛋白的序列内的保守 U_UUU_UUA 基序中发现了特定的核糖体-1 移码。在这种情况下，移码导致额外蛋白质 TF（TransFrame）的合成。这种新的移码情况不同寻常，因为-1 框 ORF 非常短，完全嵌入编码重叠多蛋白的序列中。本工作表明，在 U_UUU_UUA 基序处，对于有效移码来说，功能重要的 3'序列具有显著的多样性。虽然许多甲型病毒物种利用 3' RNA 结构（如发夹或假结），但有些物种（如 Semliki Forest 病毒）显然缺乏任何内 mRNA 刺激结构，但仅在移码位点的 3' 侧相邻 20nt 就可刺激高达 10%的移码。实验和生物信息学分析极大地扩展了哺乳动物和昆虫系统中-1 移码刺激物的已知范围。
