RNA ligases play an important role in RNA repair, thereby maintaining RNA integrity. Any malfunction in RNA repair in los seres humanos. seems to be associated with diseases like neurodegeneration and cancer. Discovery of a novel humana proteína (C12orf29 on chromosome 12) as an RNA ligase, therefore, has relevance in development of novel treatments for such diseases. Researchers have proposed to name this proteína as Homo sapiens RNA ligase (HsRnl).
La ligasa es una enzima que cataliza la unión o ligadura de dos moléculas de ácido nucleico normalmente mediante hidrólisis. Por ejemplo, la ADN ligasa facilita la unión de ADN strands by catalysing formation of phosphodiester bond thereby playing a key role maintaining genome integrity during the process of DNA replication, recombination and repair throughout the life span of the organism. Similarly, moléculas de ARN ligase catalyses the formation of phosphodiester bonds between 3′-OH and 5′-P groups of moléculas de ARN molecules. It, therefore, plays a key role in moléculas de ARN repair and maintaining cellular fitness.
La descubrimiento of C12orf29 happened while identifying AMPylated (Adenosine Mono Phosphorylated) proteínas a través del enfoque de la proteómica química1. AMPylation involves covalent attachment of AMP to proteína side chains via phosphodiester bonds in which ATP acts as a co-substrate. The proteína is 37 kDa in size and consists of 325 amino acids. Surprisingly, it is highly conserved in higher eucariotas but absent in lower eucariotas such as yeast. Functional analysis showed that it possessed 5’-3’ moléculas de ARN ligase activity. Mutational analysis revealed that changes in certain residues referring to mutations D59N, R77L, E123D, and K263N were found in patients suffering from esophageal squamous cell carcinoma, glioblastoma, chronic lymphocytic leukemia, and ovarian serous cystadenocarcinoma respectively. All the above 3 mutations except E123D lead to impaired moléculas de ARN ligadura
Knock out of C12orf29 in HEK293 (humana embryonic kidney) cells leads to vulnerability of cells towards reactive oxygen species suggesting that this proteína plays an important role in repairing damaged moléculas de ARN caused by the generation of reactive oxygen species1. Identification of this novel proteína, llamado HsRNL (Homo sapiens. moléculas de ARN ligase), has several implications in the development of novel therapeutics as impairment of moléculas de ARN repair in los seres humanos. is associated with the onset of several diseases such as neurodegeneration and cancelarr2, 3.
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Referencias:
- Yuan Y., et al 2022. A humana moléculas de ARN ligase that operates via auto- and moléculas de ARN-AMPylation. bioRxiv preprint. Posted 19 August 2022. DOI: https://doi.org/10.1101/2022.07.18.500566
- Burroughs A. M. & Aravind L. RNA damage in biological conflicts and the diversity of responding moléculas de ARN repair systems. Nucleic Acids Res. 44, 8525-8555 (2016). https://doi.org/10.1093/nar/gkw722
- Yan, L. L. & Zahner, H. S. How do cells cope with moléculas de ARN damage and its consequences? J. Biol. Chem. 294, 15158-15171 (2019). DOI: https://doi.org/10.1074/jbc.REV119.006513
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