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鉴定和表征 SARS-CoV-2 N 蛋白编码基因 RNA 结合结构域中的沉默突变。

Identification and characterization of a silent mutation in RNA binding domain of N protein coding gene from SARS-CoV-2.

机构信息

Department of Energy and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), 14965/161, Tehran, Iran.

Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.

出版信息

BMC Res Notes. 2021 Jan 6;14(1):10. doi: 10.1186/s13104-020-05439-x.

Abstract

OBJECTIVE

This study describes the occurrence of a silent mutation in the RNA binding domain of nucleocapsid phosphoprotein (N protein) coding gene from SARS-CoV-2 that may consequence to a missense mutation by onset of another single nucleotide mutation.

RESULTS

In the DNA sequence isolated from severe acute respiratory syndrome (SARS-CoV-2) in Iran, a coding sequence for the RNA binding domain of N protein was detected. The comparison of Chinese and Iranian DNA sequences displayed that a thymine (T) was mutated to cytosine (C), so "TTG" from China was changed to "CTG" in Iran. Both DNA sequences from Iran and China have been encoded for leucine. In addition, the second T in "CTG" in the DNA or uracil (U) in "CUG" in the RNA sequences from Iran can be mutated to another C by a missense mutation resulting from thymine DNA glycosylase (TDG) of human and base excision repair mechanism to produce "CCG" encoding for proline, which consequently may increase the affinity of the RNA binding domain of N protein to viral RNA and improve the transcription rate, pathogenicity, evasion from human immunity system, spreading in the human body, and risk of human-to-human transmission rate of SARS-CoV-2.

摘要

目的

本研究描述了严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)核衣壳磷酸蛋白(N 蛋白)编码基因的 RNA 结合域发生沉默突变,可能导致另一个单核苷酸突变引发错义突变。

结果

从伊朗分离的严重急性呼吸综合征(SARS-CoV-2)DNA 序列中检测到 N 蛋白 RNA 结合域的编码序列。中国和伊朗 DNA 序列的比较显示,胸腺嘧啶(T)突变为胞嘧啶(C),因此中国的“TTG”变为伊朗的“CTG”。来自伊朗和中国的两种 DNA 序列均编码为亮氨酸。此外,伊朗 DNA 序列中的“CTG”中的第二个 T 或 RNA 序列中的“CUG”中的尿嘧啶(U)可通过人类胸腺嘧啶 DNA 糖基化酶(TDG)和碱基切除修复机制发生错义突变,突变为另一个 C,产生编码脯氨酸的“CCG”,从而可能增加 N 蛋白 RNA 结合域对病毒 RNA 的亲和力,提高转录率、致病性、逃避人体免疫系统、在人体内传播以及 SARS-CoV-2 人际传播的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4afb/7788702/0cddae57fea4/13104_2020_5439_Fig1_HTML.jpg

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