Assembly of a fragmented ribonucleotide reductase by protein interaction domains derived from a mobile genetic element

Crona, Mikael,1981-Stockholms universitet,Institutionen för molekylärbiologi och funktionsgenomik,Britt-Marie Sjöberg (författare)

authorCount :6
Ribonucleotide reductase (RNR) is a critical enzyme of nucleotide metabolism, synthesizing precursors for DNA replication and repair. In prokaryotic genomes, RNR genes are commonly targeted by mobile genetic elements, including free standing and intron-encoded homing endonucleases and inteins. Here, we describe a unique molecular solution to assemble a functional product from the RNR large subunit gene, nrdA that has been fragmented into two smaller genes by the insertion of mobE, a mobile endonuclease. We show that unique sequences that originated during the mobE insertion and that are present as C- and N-terminal tails on the split NrdA-a and NrdA-b polypeptides, are absolutely essential for enzymatic activity. Our data are consistent with the tails functioning as protein interaction domains to assemble the tetrameric (NrdA-a/NrdA-b)2 large subunit necessary for a functional RNR holoenzyme. The tails represent a solution distinct from RNA and protein splicing or programmed DNA rearrangements to restore function from a fragmented coding region and may represent a general mechanism to neutralize fragmentation of essential genes by mobile genetic elements.

Sjöberg, Britt-MarieStockholms universitet,Institutionen för molekylärbiologi och funktionsgenomik(Swepub:su)bsjob (författare)
Moffatt, ConnorDepartment of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario (författare)
Edgell, David R.Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario (författare)
Friedrich, Nancy C.Department of Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario (författare)
Hofer, AndersUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)anho0002 (författare)
Stockholms universitetInstitutionen för molekylärbiologi och funktionsgenomik (creator_code:org_t)

Ingår i:Nucleic Acids Research: Oxford University Press39:4, s. 1381-13890305-10481362-4962

Av författaren/redakt...: Crona, Mikael, 1 ...; Sjöberg, Britt-M ...; Moffatt, Connor; Edgell, David R.; Friedrich, Nancy ...; Hofer, Anders

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