Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation

Catacalos, Cassandra; Krohannon, Alexander; Somalraju, Sahiti; Meyer, Kate D.; Janga, Sarath Chandra; Chakrabarti, Kausik

doi:10.1371/journal.ppat.1010972

Cited by 8 publications

(6 citation statements)

References 185 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein stability can be regulated by the ubiquitin-proteosome system ( 52 , 53 ). Recently, epitranscriptomic modifications (such as mRNA and tRNA modifications) were found to regulate RNA stability and translation efficiency ( 54 – 56 ). Many long noncoding RNAs (lncRNAs) were identified, including two lncRNAs, which regulate the transcription and/or translation of gdv1 and md1 , the regulators of gametocytogenesis and sex determination, respectively ( 57 – 59 ).…”

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Lucky,

Wang,

Shakri

et al. 2023

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Plasmodium falciparum causes the most severe malaria and is exposed to various environmental and physiological stresses in the human host. Given that GCN5 plays a critical role in regulating stress responses in model organisms, we aimed to elucidate PfGCN5’s function in stress responses in P. falciparum . The protein level of PfGCN5 was substantially induced under three stress conditions [heat shock, low glucose starvation, and dihydroartemisinin, the active metabolite of artemisinin (ART)]. With a TetR-DOZI conditional knockdown (KD) system, we successfully down-regulated PfGCN5 to ~50% and found that KD parasites became more sensitive to all three stress conditions. Transcriptomic analysis via RNA-seq identified ~1,000 up- and down-regulated genes in the wild-type (WT) and KD parasites under these stress conditions. Importantly, DHA induced transcriptional alteration of many genes involved in many aspects of stress responses, which were heavily shared among the altered genes under heat shock and low glucose conditions, including ART-resistance-related genes such as K13 and coronin . Based on the expression pattern between WT and KD parasites under three stress conditions, ~300–400 genes were identified to be involved in PfGCN5-dependent, general, and stress-condition-specific responses with high levels of overlaps among three stress conditions. Notably, using ring-stage survival assay, we found that KD or inhibition of PfGCN5 could sensitize the ART-resistant parasites to the DHA treatment. All these indicate that PfGCN5 is pivotal in regulating general and ART-resistance-related stress responses in malaria parasites, implicating PfGCN5 as a potential target for malaria intervention.

show abstract

Section: Discussionmentioning

confidence: 99%

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Lucky,

Wang,

Shakri

et al. 2023

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Important future areas of study include how widespread METTL3 orthologs are in human parasites and the prevalence of m 6 A methylome changes for host and parasitic RNAs. Please refer to a review by Catacalos et al for more details on the biology of m 6 A in parasites (Catacalos et al, 2022).…”

Section: Roles Of M 6 a Mtases In Infectious Agents: Viruses And Para...mentioning

confidence: 99%

Ghost authors revealed: The structure and function of human N⁶‐methyladenosine RNA methyltransferases

Breger,

Kunkler,

O'Leary

et al. 2023

WIREs RNA

View full text Add to dashboard Cite

Despite the discovery of modified nucleic acids nearly 75 years ago, their biological functions are still being elucidated. N6‐methyladenosine (m6A) is the most abundant modification in eukaryotic messenger RNA (mRNA) and has also been detected in non‐coding RNAs, including long non‐coding RNA, ribosomal RNA, and small nuclear RNA. In general, m6A marks can alter RNA secondary structure and initiate unique RNA–protein interactions that can alter splicing, mRNA turnover, and translation, just to name a few. Although m6A marks in human RNAs have been known to exist since 1974, the structures and functions of methyltransferases responsible for writing m6A marks have been established only recently. Thus far, there are four confirmed human methyltransferases that catalyze the transfer of a methyl group from S‐adenosylmethionine (SAM) to the N6 position of adenosine, producing m6A: methyltransferase‐like protein (METTL) 3/METTL14 complex, METTL16, METTL5, and zinc‐finger CCHC‐domain‐containing protein 4. Though the methyltransferases have unique RNA targets, all human m6A RNA methyltransferases contain a Rossmann fold with a conserved SAM‐binding pocket, suggesting that they utilize a similar catalytic mechanism for methyl transfer. For each of the human m6A RNA methyltransferases, we present the biological functions and links to human disease, RNA targets, catalytic and kinetic mechanisms, and macromolecular structures. We also discuss m6A marks in human viruses and parasites, assigning m6A marks in the transcriptome to specific methyltransferases, small molecules targeting m6A methyltransferases, and the enzymes responsible for hypermodified m6A marks and their biological functions in humans. Understanding m6A methyltransferases is a critical steppingstone toward establishing the m6A epitranscriptome and more broadly the RNome.This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Recognition RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications

show abstract

“…This seminal work paved the way for the discovery of m 6 A in viral RNAs [ 19 , 20 ], including the influenza A virus (IAV) exhibiting similar m 6 A levels to cellular RNA. Over the decades, the multifaceted role of m 6 A in regulating gene expression, especially its influence on various stages of viral lifecycle and host–virus interactions, has been gradually elucidated [ 21 ]. A detailed description of this topic is beyond the scope of this review, and we refer interested readers to some recent comprehensive reviews [ 11 , 12 , 16 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Decoding epitranscriptomic regulation of viral infection: mapping of RNA N6-methyladenosine by advanced sequencing technologies

Fan,

Zhang,

Guo

et al. 2024

Cell Mol Biol Lett

View full text Add to dashboard Cite

Elucidating the intricate interactions between viral pathogens and host cellular machinery during infection is paramount for understanding pathogenic mechanisms and identifying potential therapeutic targets. The RNA modification N6-methyladenosine (m6A) has emerged as a significant factor influencing the trajectory of viral infections. Hence, the precise and quantitative mapping of m6A modifications in both host and viral RNA is pivotal to understanding its role during viral infection. With the rapid advancement of sequencing technologies, scientists are able to detect m6A modifications with various quantitative, high-resolution, transcriptome approaches. These technological strides have reignited research interest in m6A, underscoring its significance and prompting a deeper investigation into its dynamics during viral infections. This review provides a comprehensive overview of the historical evolution of m6A epitranscriptome sequencing technologies, highlights the latest developments in transcriptome-wide m6A mapping, and emphasizes the innovative technologies for detecting m6A modification. We further discuss the implications of these technologies for future research into the role of m6A in viral infections. Graphical Abstract

show abstract

Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation

Cited by 8 publications

References 185 publications

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Ghost authors revealed: The structure and function of human N⁶‐methyladenosine RNA methyltransferases

Decoding epitranscriptomic regulation of viral infection: mapping of RNA N6-methyladenosine by advanced sequencing technologies

Contact Info

Product

Resources

About

Epitranscriptomics in parasitic protists: Role of RNA chemical modifications in posttranscriptional gene regulation

Cited by 8 publications

References 185 publications

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Plasmodium falciparum GCN5 plays a key role in regulating artemisinin resistance-related stress responses

Ghost authors revealed: The structure and function of human N6‐methyladenosine RNA methyltransferases

Decoding epitranscriptomic regulation of viral infection: mapping of RNA N6-methyladenosine by advanced sequencing technologies

Contact Info

Product

Resources

About

Ghost authors revealed: The structure and function of human N⁶‐methyladenosine RNA methyltransferases