DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Март 31, 2023

Abstract Non-obstructive azoospermia, the absence of sperm in ejaculate due to disturbed spermatogenesis, represents most severe form male infertility. De novo microdeletions Y-chromosomal AZFa region are one few well-established genetic causes for NOA and routinely analysed diagnostic workup affected men. So far, it is unclear which three genes located chromosomal indispensible germ cell maturation. Here we present four different likely pathogenic loss-of-function variants gene DDX3Y identified by analysing exome sequencing data more than 1,600 infertile Three patients underwent testicular extraction revealed typical Sertoli cell-only phenotype. One was proven be de novo. Consequently, key spermatogenic factor screening should included workflow.

Язык: Английский

---

Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states

Cell chemical biology, Год журнала: 2024, Номер 31(1), С. 17 - 35

Опубликована: Янв. 1, 2024

Язык: Английский

---

DDX3X and Stress Granules: Emerging Players in Cancer and Drug Resistance

Cancers, Год журнала: 2024, Номер 16(6), С. 1131 - 1131

Опубликована: Март 12, 2024

The DEAD (Asp-Glu-Ala-Asp)-box helicase 3 X-linked (DDX3X) protein participates in many aspects of mRNA metabolism and stress granule (SG) formation. DDX3X has also been associated with signal transduction cell cycle regulation that are important maintaining cellular homeostasis. Malfunctions have implicated multiple cancers, including brain cancer, leukemia, prostate head neck cancer. Recently, literature reported SG-associated cancer drug resistance, which correlates a negative disease prognosis. Based on the connections between DDX3X, SG formation, pathology, targeting may be promising direction for therapeutics development. In this review, we describe biological functions terms metabolism, transduction, regulation. Furthermore, summarize contributions formation adaptation. Finally, discuss relationships SG, current research progress several inhibitors treatment.

Язык: Английский

---

The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles

Annual Review of Biochemistry, Год журнала: 2024, Номер 93(1), С. 79 - 108

Опубликована: Апрель 10, 2024

DEAD- and DExH-box ATPases (DDX/DHXs) are abundant highly conserved cellular enzymes ubiquitously involved in RNA processing. By remodeling RNA–RNA RNA–protein interactions, they often function as gatekeepers that control the progression of diverse maturation steps. Intriguingly, most DDX/DHXs localize to membraneless organelles (MLOs) such nucleoli, nuclear speckles, stress granules, or processing bodies. Recent findings suggest not only localization MLOs can promote interaction between their targets but also key regulators MLO formation turnover through condensation ATPase activity.In this review, we describe molecular ribosome biogenesis, messenger splicing, export, translation, storage decay well association with prominent MLOs. We discuss how enzymatic is linked DDX/DHX condensation, accumulation ribonucleoprotein particles dynamics. Future research will reveal these processes orchestrate life cycle space time.

Язык: Английский

---

Non-AUG HIV-1 uORF translation elicits specific T cell immune response and regulates viral transcript expression

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 18, 2025

Human immunodeficiency virus type-1 (HIV-1) is a complex retrovirus that relies on alternative splicing, translational, and post-translational mechanisms to produce over 15 functional proteins from its single ~10 kb transcriptional unit. Using ribosome profiling, nascent protein labeling, RNA sequencing, whole-proteomics of infected CD4 + T lymphocytes, we characterized the transcriptional, landscape during infection. While viral infection exerts significant impact host transcript abundance, global translation rates are only modestly affected. Proteomics data reveal extensive regulation, with many genes showing opposing trends between transcript/ribosome profiling abundance. These findings highlight regulatory network orchestrating gene expression at multiple levels. Viral further uncovered non-AUG small peptides upstream open reading frames (uORFs) within 5' long terminal repeat, which elicit specific cell responses in people living HIV. Conservation uORF among retroviruses, along TAR sequences, shapes DDX3 dependency for efficient main frames. Here, integrating RNA-seq proteomics regulation HIV-infected cells, authors show ORFs elicits distinct immune regulates DDX3-dependent manner.

Язык: Английский

---

Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A

Cell chemical biology, Год журнала: 2020, Номер 28(4), С. 475 - 486.e8

Опубликована: Дек. 8, 2020

Язык: Английский

---

Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP

Genome biology, Год журнала: 2022, Номер 23(1)

Опубликована: Сен. 9, 2022

Crosslinking and immunoprecipitation (CLIP) is a method used to identify in vivo RNA-protein binding sites on transcriptome-wide scale. With the increasing amounts of available data for RNA-binding proteins (RBPs), it important understand what degree enriched motifs specify profiles RBPs cells.

Язык: Английский

---

The human DEAD-box helicase DDX3X as a regulator of mRNA translation

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Окт. 25, 2022

The human DEAD-box protein DDX3X is an RNA remodelling enzyme that has been implicated in various aspects of metabolism. In addition, like many proteins, it non-conventional functions are independent its enzymatic activity, e.g., acts as adaptor molecule innate immune signalling pathways. linked to several diseases. For example, somatic mutations were identified cancers, and de novo germline cause a neurodevelopmental condition now termed ‘DDX3X syndrome’. also important host factor different viral infections, where can have pro-or anti-viral effects depending on the specific virus. regulation translation initiation for mRNA transcripts likely central cellular function DDX3X, yet questions regarding exact targets mechanisms action remain unanswered. this review, we explore current knowledge about DDX3X’s physiological summarise interactions with machinery. A role translational reprogramming during stress emerging, may be involved granule formation mediating non-canonical initiation. Finally, discuss DDX3X-mediated infections. Dysregulation contributes involvement disease pathophysiology. Thus, better understanding regulating important, so potentially develop therapeutic strategies overcoming negative dysregulation.

Язык: Английский

---

Identification of RNA helicases with unwinding activity on angiogenin-processed tRNAs

Nucleic Acids Research, Год журнала: 2023, Номер 51(3), С. 1326 - 1352

Опубликована: Янв. 31, 2023

Abstract Stress-induced tRNA fragmentation upon environmental insult is a conserved cellular process catalysed by endonucleolytic activities targeting mature tRNAs. The resulting tRNA-derived small RNAs (tsRNAs) have been implicated in various biological processes that impact cell-to-cell signalling, cell survival as well gene expression regulation during embryonic development. However, how endonuclease-targeted tRNAs give rise to individual and potentially biologically active tsRNAs remains poorly understood. Here, we report on the vivo identification of proteins associated with stress-induced tsRNAs-containing protein complexes, which, together ‘tracer tRNA’ assay, were used uncover enzymatic can bind specific vitro. Among those, identified ATP-dependent RNA helicases which robustly separate endonuclease-mediated ‘nicks’ their anticodon loops. These findings shed light existence pathways dedicated producing after hydrolysis, adds our understanding might exert physiological impact.

Язык: Английский

---

The variant landscape and function of DDX3X in cancer and neurodevelopmental disorders

Trends in Molecular Medicine, Год журнала: 2023, Номер 29(9), С. 726 - 739

Опубликована: Июль 6, 2023

RNA molecules rely on proteins across their life cycle. DDX3X encodes an X-linked DEAD-box helicase with a Y-linked paralog, DDX3Y. is central to the cycle and implicated in many conditions, including cancer neurodevelopmental disorder syndrome. DDX3X-linked conditions often exhibit sex differences, possibly due differences between expression or function of X- paralogs DDX3X-related diseases have different mutational landscapes, indicating roles DDX3X. Understanding role normal disease states will inform understanding disease. We review DDX3Y, discuss how mutation type bias contribute human involving DDX3X, possible DDX3X-targeting treatments.

Язык: Английский

---