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RNA-editing substrate-binding complex subunit 1 (RESC1) and RESC2 RESC1 (GRBC1, GAP2) and RESC2 (GRBC2, GAP1) form a stable heterotetramer that directly binds guide RNAs (gRNAs) and is essential for the stability of gRNAs in U-insertion/deletion mRNA editing during kinetoplast RNA processing. The mitochondrial DNA of Trypanosomatids, known as the kinetoplast DNA (kDNA or mtDNA), consists of a network of dozens of maxicircles and thousands of minicircles concatenated together. Maxicircles are equivalent to other eukaryotic mitochondrial DNAs, while minicircles encode guide RNAs (gRNAs) involved in U-insertion/deletion editing processes exclusive of Trypanosomatids that produce the maturation of the maxicircle-encoded transcripts. Although most gRNAs are encoded by minicircles, varying numbers of maxicircle-encoded gRNAs have been identified in kinetoplastids species. Trypanosoma brucei maxicircles encode 9S and 12S rRNAs, two gRNAs, two ribosomal proteins and 16 subunits of respiratory complexes. 12 of the 18 maxicircle genes are present as cryptogenes whose transcripts require U-insertion/deletion editing, mediated by gRNAs, to restore a protein-coding capacity. RESC1/2 is a core component of the RNA-editing substrate-binding complex (RESC) that consists of about 20 components. RESC interacts with two other complexes, the RNA-editing helicase 2 complex (REH2C) and RNA-editing catalytic complex (RECC) to form an assembly (editosome/holoenzyme) that carries out U-insertion/deletion mRNA editing. The predicted structures (by AlphaFold) of RESC1 and RESC2 contain a domain most structurally similar to fungal mRNA triphosphatases belonging to the CYTH-like (also known as triphosphate tunnel metalloenzyme (TTM)-like) phosphatase superfamily; this domain adopts an eight-stranded antiparallel beta barrel tunnel (the triphosphate tunnel) with an active site located at the center of the tunnel. mRNA triphosphatase catalyzes the first step in the mRNA cap formation process, the removal of the gamma-phosphate of triphosphate terminated pre-mRNA. RESC1/2 lack the conserved mRNA triphosphatase active site residues and may not exhibit this enzymatic activity. |
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Jiyao W et al.(2023). "The conserved domain database in 2023.",