Institute for Biochemistry, Leipzig University, Brüderstraße 34, 04103 Leipzig, Germany.
Bioinformatics Group, Department of Computer Science and Interdisciplinary Centre for Bioinformatics, Leipzig University, Härtelstraße 16-18, 04107 Leipzig, Germany.
Nucleic Acids Res. 2021 Jun 21;49(11):6375-6388. doi: 10.1093/nar/gkab454.
Self-cleaving ribozymes are catalytic RNAs that cut themselves at a specific inter-nucleotide linkage. They serve as a model of RNA catalysis, and as an important tool in biotechnology. For most of the nine known structural classes of self-cleaving ribozymes, at least hundreds of examples are known, and some are present in multiple domains of life. By contrast, only four unique examples of the hairpin ribozyme class are known, despite its discovery in 1986. We bioinformatically predicted 941 unique hairpin ribozymes of a different permuted form from the four previously known hairpin ribozymes, and experimentally confirmed several diverse predictions. These results profoundly expand the number of natural hairpin ribozymes, enabling biochemical analysis based on natural sequences, and suggest that a distinct permuted form is more biologically relevant. Moreover, all novel hairpins were discovered in metatranscriptomes. They apparently reside in RNA molecules that vary both in size-from 381 to 5170 nucleotides-and in protein content. The RNA molecules likely replicate as circular single-stranded RNAs, and potentially provide a dramatic increase in diversity of such RNAs. Moreover, these organisms have eluded previous attempts to isolate RNA viruses from metatranscriptomes-suggesting a significant untapped universe of viruses or other organisms hidden within metatranscriptome sequences.
自我剪切核酶是一种能够在特定核苷酸连接处自我切割的催化 RNA。它们是 RNA 催化的模型，也是生物技术中的重要工具。对于已知的九种自我剪切核酶结构类型中的大多数，至少有数百个已知的例子，并且有些存在于生命的多个领域。相比之下，尽管发现在 1986 年，但仅发现了四个独特的发夹核酶类。我们通过生物信息学预测了从四个先前已知的发夹核酶中不同排列形式的 941 个独特的发夹核酶，并通过实验证实了几个不同的预测。这些结果极大地扩展了天然发夹核酶的数量，使基于天然序列的生化分析成为可能，并表明独特的排列形式更具生物学相关性。此外，所有新的发夹都在宏转录组中发现。它们显然存在于 RNA 分子中，这些 RNA 分子的大小差异很大-从 381 到 5170 个核苷酸-并且蛋白质含量也不同。这些 RNA 分子可能作为环状单链 RNA 进行复制，并有可能大大增加此类 RNA 的多样性。此外，这些生物体逃避了先前试图从宏转录组中分离 RNA 病毒的尝试-这表明宏转录组序列中隐藏着大量未开发的病毒或其他生物体。
