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人类微小RNA对恶性疟原虫基因表达调控的预测

Prediction of gene expression regulation by human microRNAs in Plasmodium falciparum.

作者信息

Grinev Alexandr, Fokina Natalya, Bogomolov Denis, Berechikidze Iza, Lazareva Yuliya

机构信息

Department of Biology and General Genetics, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

出版信息

Genes Environ. 2021 Jun 15;43(1):22. doi: 10.1186/s41021-021-00198-y.

Abstract

BACKGROUND

Malaria is a disease annually causing over 400,000 deaths. Deep understanding of molecular and genetic processes underlying its life cycle and pathogenicity is required to efficiently resist it. RNA interference is a mechanism of the gene expression regulation typical for a wide variety of species. Even though the existence of this phenomenon in Plasmodium falciparum has long been rejected, several recent works pose hypotheses and provide direct and indirect evidence of the existence of mechanisms similar to RNA interference in this organism. In particular, the possibility of regulation of P. falciparum gene expression through human microRNAs is of great importance both for fundamental biology and for medicine. In the present work we address the problem of possibility of the existence in the P. falciparum genome of the nucleotide sequences such that mRNAs transcribed from genes containing these sequences could form duplexes with human microRNAs. Using bioinformatics methods we have analysed genomes of 15 P. falciparum isolates for sequences homological to these microRNAs.

RESULTS

The analysis has demonstrated the existence of a vast number of genes that could potentially be regulated by the human microRNAs in the plasmodial genome.

CONCLUSIONS

Despite the fact that the numbers of homological intervals vary significantly between isolates, the hsa-miR-451a and hsa-miR-223-3p microRNAs are expected to make the most notable contribution to the pathogenesis of P. falciparum malaria. The majority of homological intervals occur in genes encoding cell adhesion proteins.

摘要

背景

疟疾是一种每年导致超过40万例死亡的疾病。为了有效抵抗疟疾,需要深入了解其生命周期和致病性背后的分子和遗传过程。RNA干扰是多种物种中典型的基因表达调控机制。尽管长期以来人们一直否认恶性疟原虫中存在这种现象,但最近的几项研究提出了假设,并提供了该生物体中存在类似于RNA干扰机制的直接和间接证据。特别是,通过人类微小RNA调控恶性疟原虫基因表达的可能性,对基础生物学和医学都具有重要意义。在本研究中,我们探讨了恶性疟原虫基因组中是否存在核苷酸序列,使得从包含这些序列的基因转录的mRNA能够与人类微小RNA形成双链体的问题。我们使用生物信息学方法分析了15个恶性疟原虫分离株的基因组,以寻找与这些微小RNA同源的序列。

结果

分析表明,疟原虫基因组中存在大量可能受人类微小RNA调控的基因。

结论

尽管不同分离株之间同源区间的数量差异显著,但预计hsa-miR-451a和hsa-miR-223-3p微小RNA对恶性疟原虫疟疾的发病机制贡献最大。大多数同源区间出现在编码细胞粘附蛋白的基因中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb91/8204574/da3e0a5fbd8f/41021_2021_198_Fig1_HTML.jpg

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