DEAH-Box RNA Helicases in Pre-mRNA Splicing

Bortoli, Francesca De; Espinosa, Sara; Zhao, Rui

doi:10.1016/j.tibs.2020.10.006

Cited by 47 publications

(40 citation statements)

References 85 publications

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“…The spliceosome undergoes extensive conformational and compositional rearrangements that are catalyzed by eight RNA helicases of the DExD/H family ( De Bortoli et al 2021 ). The activity of DEAH RNA helicases, such as DHX34, is often regulated through G-patch proteins, which function as adaptors that recruit them to functional sites and enhance their activity ( Studer et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…A common function for RNA helicases is in the process of pre-mRNA splicing, where eight conserved DExD/H RNA helicases have been shown to play essential roles in directing conformational rearrangements in the spliceosome. These include DDX46/Prp5, DDX39B/Sub2, and DDX23/Prp28 that belong to the DEAD-box family; DHX8/Prp22, DHX15/Prp43, DHX16/Prp2, and DHX38/Prp16 that belong to the DEAH-box family and SNRNP200/Brr2 that is part of the Ski-2 like family ( Cordin and Beggs 2013 ; Bourgeois et al 2016 ; De Bortoli et al 2021 ). The function of these RNA helicases in constitutive splicing is diverse since they affect different steps of the spliceosomal cycle.…”

Section: Introductionmentioning

confidence: 99%

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A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation

Hug

Aitken

Longman

et al. 2022

RNA

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The DExD/H-box RNA helicase DHX34 is a nonsense-mediated decay (NMD) factor that together with core NMD factors coregulates NMD targets in nematodes and in vertebrates. Here, we show that DHX34 is also associated with the human spliceosomal catalytic C complex. Mapping of DHX34 endogenous binding sites using cross-linking immunoprecipitation (CLIP) revealed that DHX34 is preferentially associated with pre-mRNAs and locates at exon–intron boundaries. Accordingly, we observed that DHX34 regulates a large number of alternative splicing (AS) events in mammalian cells in culture, establishing a dual role for DHX34 in both NMD and pre-mRNA splicing. We previously showed that germline DHX34 mutations associated to familial myelodysplasia (MDS)/acute myeloid leukemia (AML) predisposition abrogate its activity in NMD. Interestingly, we observe now that DHX34 regulates the splicing of pre-mRNAs that have been linked to AML/MDS predisposition. This is consistent with silencing experiments in hematopoietic stem/progenitor cells (HSPCs) showing that loss of DHX34 results in differentiation blockade of both erythroid and myeloid lineages, which is a hallmark of AML development. Altogether, these data unveil new cellular functions of DHX34 and suggest that alterations in the levels and/or activity of DHX34 could contribute to human disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation

Hug

Aitken

Longman

et al. 2022

RNA

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“…In eukaryotes, many helicases involved in splicing are well conserved [ 98 ]. They are able to unwind RNA structures and thus initiate conformational rearrangements [ 99 ].…”

Section: Evolution and Function Of Nuclear Splicing Factorsmentioning

confidence: 99%

The Chloroplast Trans-Splicing RNA–Protein Supercomplex from the Green Alga Chlamydomonas reinhardtii

Kück

Schmitt

2021

Cells

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In eukaryotes, RNA trans-splicing is a significant RNA modification process for the end-to-end ligation of exons from separately transcribed primary transcripts to generate mature mRNA. So far, three different categories of RNA trans-splicing have been found in organisms within a diverse range. Here, we review trans-splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. We discuss the origin of intronic sequences and the evolutionary relationship between chloroplast ribonucleoprotein complexes and the nuclear spliceosome. Finally, we focus on the ribonucleoprotein supercomplex involved in trans-splicing of chloroplast group II introns from the green alga Chlamydomonas reinhardtii. This complex has been well characterized genetically and biochemically, resulting in a detailed picture of the chloroplast ribonucleoprotein supercomplex. This information contributes substantially to our understanding of the function of RNA-processing machineries and might provide a blueprint for other splicing complexes involved in trans- as well as cis-splicing of organellar intron RNAs.

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“…Both families bear the Asp-Glu-X-Asp/His signature. A highly conserved helicase core domain consists of two linked RecA-like domains, harboring at least twelve conserved motifs involved in Adenosine triphosphate (ATP) binding/hydrolysis and Ribonucleic acid (RNA) binding [ 2 – 4 ]. RNAs interact with both RecA-like domains along the sugar-phosphate backbone, explaining why DExD/H-box helicases’ binding to RNA is generally sequence-independent but structure-dependent.…”

Section: Introductionmentioning

confidence: 99%

DExD/H-box helicases: multifunctional regulators in antiviral innate immunity

Tang

Zheng

2021

Cell. Mol. Life Sci.

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DExD/H-box helicases play critical roles in multiple cellular processes, including transcription, cellular RNA metabolism, translation, and infections. Several seminal studies over the past decades have delineated the distinct functions of DExD/H-box helicases in regulating antiviral innate immune signaling pathways, including Toll-like receptors, retinoic acid-inducible gene I-like receptors, cyclic GMP-AMP synthase-the stimulator of interferon gene, and NOD-like receptors signaling pathways. Besides the prominent regulatory roles, there is increasing attention on their functions as nucleic acid sensors involved in antiviral innate immunity. Here we summarize the complex regulatory roles of DExD/H-box helicases in antiviral innate immunity. A better understanding of the underlying molecular mechanisms of DExD/H-box helicases’ regulatory roles is vital for developing new therapeutics targeting DExD/H-box helicases and their mediated signaling transduction in viral infectious diseases.

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DEAH-Box RNA Helicases in Pre-mRNA Splicing

Cited by 47 publications

References 85 publications

A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation

A dual role for the RNA helicase DHX34 in NMD and pre-mRNA splicing and its function in hematopoietic differentiation

The Chloroplast Trans-Splicing RNA–Protein Supercomplex from the Green Alga Chlamydomonas reinhardtii

DExD/H-box helicases: multifunctional regulators in antiviral innate immunity

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