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In Escherichia coli, the Nudix hydrolase RppH initiates mRNA degradation by removing pyrophosphate from mRNA 5\u2032-ends, converting 5\u2032-triphosphates to 5\u2032-monophosphates. We aimed to identify the RppH homolog in the globally important pathogen Mycobacterium tuberculosis (Mtb). We identified the protein encoded by Rv3908, previously annotated as a nucleotide pool cleanser mutT4, as the predominant mycobacterial RppH. Deletion of rppHMtb increased the relative abundance of 5\u2032-triphosphates on myriad mRNAs across the transcriptome. Purified RppHMtb converted mRNA 5\u2032-triphosphates into monophosphates, and stimulated degradation by RNase E and RNase J in vitro to varying extents. Surprisingly, deletion of rppHMtb had mixed impacts on mRNA degradation in vivo, suggesting that it may not sensitize most transcripts to degradation. RppHMtb has intrinsically disordered regions (IDRs), which often participate in biomolecular condensate formation. Microscopy showed that RppHMtb forms condensate-like bodies that localize with RNases and dissociate upon addition of rifampicin. The N-terminal IDR is sufficient for condensate-like body formation. Deletion of rppHMtb leads to higher outer membrane permeability and resistance to oxidative stress. We conclude that MutT4 is the mycobacterial RppH, assembling in condensate-like bodies with RNases but having unexpectedly complex impacts on mRNA degradation rates.<\/jats:p>","DOI":"10.1093\/nar\/gkag200","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:44:49Z","timestamp":1772023489000},"source":"Crossref","is-referenced-by-count":3,"title":["<i>Mycobacterium tuberculosis<\/i>\n                    MutT4\/RppH is an RNA pyrophosphohydrolase that forms condensate-like bodies and impacts mRNA degradation"],"prefix":"10.1093","volume":"54","author":[{"given":"J Hilario","family":"Cafiero","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute , Worcester, MA 01609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Program in Bioinformatics and Computational Biology, Worcester Polytechnic Institute , Worcester, MA 01609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Lepori","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Amherst , Amherst, MA 01003 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R","family":"Rapiejko","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute , Worcester, MA 01609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manchi","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&M University, College Station , TX 77840 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opeyemi I","family":"Ibitoye","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute , Worcester, MA 01609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis A","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnology, Worcester Polytechnic Institute , Worcester, MA 01609 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C","family":"Sacchettini","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, Texas A&M University, College Station , TX 77840 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Sloan","family":"Siegrist","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Massachusetts Amherst , Amherst, MA 01003 ,","place":["United States"]},{"name":"Molecular and 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