Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells

Enrique I Ramos; Raja Veerapandian; Kishore Das; Jessica A Chacon; Shrikanth S Gadad; Subramanian Dhandayuthapani

doi:10.1016/j.ncrna.2023.03.002

Pathogenic mycoplasmas of humans regulate the long noncoding RNAs in epithelial cells

Noncoding RNA Res. 2023 Mar 8;8(3):282-293. doi: 10.1016/j.ncrna.2023.03.002. eCollection 2023 Sep.

Authors

Enrique I Ramos¹, Raja Veerapandian², Kishore Das², Jessica A Chacon³, Shrikanth S Gadad^{1

4

5}, Subramanian Dhandayuthapani^{2

4}

Affiliations

¹ Center of Emphasis in Cancer, Department of Molecular and Translational Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA.
² Center of Emphasis in Infectious Diseases, Paul L. Foster School of Medicine, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA.
³ Department of Medical Education, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center El Paso, TX, 79905, USA.
⁴ Frederick L. Francis Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, Texas, 79905, USA.
⁵ Mays Cancer Center, UT Health San Antonio MD Anderson Cancer Center, San Antonio, TX, 78229, USA.

Abstract

Non-coding RNAs (ncRNAs), specifically long ncRNAs (lncRNAs), regulate cellular processes by affecting gene expression at the transcriptional, post-transcriptional, and epigenetic levels. Emerging evidence indicates that pathogenic microbes dysregulate the expression of host lncRNAs to suppress cellular defense mechanisms and promote survival. To understand whether the pathogenic human mycoplasmas dysregulate host lncRNAs, we infected HeLa cells with Mycoplasma genitalium (Mg) and Mycoplasma penumoniae (Mp) and assessed the expression of lncRNAs by directional RNA-seq analysis. HeLa cells infected with these species showed up-and-down regulation of lncRNAs expression, indicating that both species can modulate host lncRNAs. However, the number of upregulated (200 for Mg and 112 for Mp) and downregulated lncRNAs (30 for Mg and 62 for Mp) differ widely between these two species. GREAT analysis of the noncoding regions associated with differentially expressed lncRNAs showed that Mg and Mp regulate a discrete set of lncRNA plausibly related to transcription, metabolism, and inflammation. Further, signaling network analysis of the differentially regulated lncRNAs exhibited diverse pathways such as neurodegeneration, NOD-like receptor signaling, MAPK signaling, p53 signaling, and PI3K signaling, suggesting that both species primarily target signaling mechanisms. Overall, the study's results suggest that Mg and Mp modulate lncRNAs to promote their survival within the host but in distinct manners.

Keywords: Epithelial cells; Gene expression analyses; Long non-coding RNAs; Mycoplasma.

Abstract

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