The seminal discovery of ribonuclease P (RNase P) and its catalytic RNA by Sidney Altman has not only revolutionized our understanding of life, but also opened new fields for scientific exploration and investigation. This review focuses on human RNase P and its use as a gene-targeting tool, two topics initiated in Altman’s laboratory. We outline early works on human RNase P as a tRNA processing enzyme and comment on its expanding nonconventional functions in molecular networks of transcription, chromatin remodeling, homology-directed repair, and innate immunity. The important implications and insights from these discoveries on the potential use of RNase P as a gene-targeting tool are presented. This multifunctionality calls to a modified structure–function partitioning of domains in human RNase P, as well as its relative ribonucleoprotein, RNase MRP. The role of these two catalysts in innate immunity is of particular interest in molecular evolution, as this dynamic molecular network could have originated and evolved from primordial enzymes and sensors of RNA, including predecessors of these two ribonucleoproteins.
Bibliographical noteFunding Information:
We thank Paul S. Eder (NIH) for valuable comments and editing of the manuscript, and Isadora Zhang and Eduardo Lujan for critical reading and comments. This research was supported by the Israel Science Foundation (#538/21 and #1205/17) and the United States-Israel Binational Science Foundation (#2015/157) to N.J. and by a University of California Start-Up Fund to F.L. This essay is dedicated to the memory of Sidney Altman, a supreme scientist and caring mentor.
© 2023 Jarrous and Liu This article, published in RNA.
- RNA polymerase III
- RNase P
- gene targeting
- innate immunity