Editorial [Hot Topic: Highly Sequence-Specific Endoribonucleases (Guest Editor: Fakhri Saida )]

Inactivation of RNA molecules by sequence-specific endoribonucleolytic cleavage is a subtle mechanism by which cells coordinate, regulate and adapt their complex gene expression patterns. This special issue entitled “Highly Sequence-Specific Endoribonucleases” highlights the latest findings in the field of RNA recognition and cleavage by sequence-specific endoribonucleases. The aim of this issue is not to provide an exhaustive collection of sequence-specific endoribonucleases but rather present an updated, hopefully general, view on how these particular enzymes work. Our main goal is to attract the attention of the audience to the exquisite molecular details that allow these endoribonucleases to recognize and cleave particular phosphodiester bonds confined within hundreds, sometimes thousands, of chemically similar bonds.

This special issue opens with a manuscript analyzing and comparing structural and biochemical data from nine highly sequence-specific endoribonucleases that target messenger, ribosomal and transfer RNA molecules. A special emphasis is given to phage T4 endoribonuclease RegB and is based on our recently published solution structure of the enzyme. This manuscript is aimed to show that despite the absence of any relevant sequence similarities, even between functionally related ribonucleases, and the wide variety of biological sources; the analyzed sequence-specific endoribonucleases adopt limited structural folds, catalyze their cleavage reaction using the same chemistry and use a small set of amino acids for both RNA recognition and cleavage.

Following this analysis is a manuscript that reviews structural and functional data, obtained by the R. Boelens group, for sequence-specific endoribonuclease Kid and its specific inhibitor Kis. The authors compare the properties of their Kid-Kis system to other known bacterial toxin-antitoxin systems.

A third manuscript is dedicated to ribotoxin restrictocin. This manuscript presents original research results dealing with the role of particular residues in loops L2 and L4 in the activity of restrictocin.

The fourth manuscript treats the case of endoribonuclease ErEN. This enzyme can destabilize α -globin mRNA through a sequence-specific cleavage in its 3' untranslated region. Interestingly, a multi-protein complex is reported to regulate the activity of this endoribonuclease.

The fifth manuscript deals with tRNase Z. The authors describe the diversity of tRNase Z activities, the structural basis for substrate specificity and the potential application of the enzyme for sequence-specific cleavage of target RNA molecules.

The manuscript written by K. Chak describes an unusual sequence-specific ribonuclease activity derived from the dimeric interface of the ImE7 protein (a protein encoded in the ColE7 operon). Although the exact identity of this ribonuclease activity is still elusive, the authors show strong evidences for the involvement of ImE7 in the regulation of the stability of its own mRNA through a sequence-specific cleavage.

The manuscript by L. Koroleva presents a detailed and comprehensive view of the recent advances in the design of metalfree ribonuclease mimics as well as sequence-specific oligonucleotide-based artificial ribonucleases.

I hope that the audience will find in this selection of papers not only a summary of the present understanding on how sequence-specific endoribonucleases work but also an invitation for future investigations in this exciting field.

Finally, I express my gratitude to all contributing authors and reviewers and to Protein & Peptide Letters for giving me the chance to compose this special issue.