A Distinct Mechanism of RNA Recognition by the Transcription Factor GATA1

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Several human transcription factors (TFs) have been reported to directly bind RNA through noncanonical RNA-binding domains; however, most of these TFs remain be further validated as bona fide proteins (RBPs). Our systematic analysis RBP discovery data sets reveals a varied set candidate TF-RBPs that encompass TF families. These RBPs include members the GATA family are essential in embryonic development. Investigation features GATA1, major hematopoietic TF, robust sequence independent binding RNAs vitro. Moreover, by GATA1 is competitive with DNA binding, which occurs shared surface spanning DNA-binding domain and arginine-rich motif (ARM)-like domain. We show ARM-like contributes substantially high-affinity electrostatically plastic recognition, suggesting separable assigned ARM-domain an oversimplification more complex recognition network. biochemical demonstrate unified integration DNA- surfaces within whereby provides electrostatic for but does not fully dominate GATA1-RNA interactions, may also apply other TF-RBPs. This DNA/RNA activity using overlapping nucleic acid regions points possibility RNA-mediated regulation function during hematopoiesis. study highlights multifunctionality domains supports need characterization predicted such domains.

Язык: Английский

---

Longitudinal and large-scale monitoring of transcriptome and RBP-RNA interactome in living cells by engineered protein nanocages

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Nondestructive sequencing of RNA from live cells is essential for monitoring and understanding dynamic biological processes. However, most existing methods rely on cell lysis or fixation, limiting their applicability longitudinal studies. Here, we introduce POND-seq (Protein nanocage-empOwered Non-Destructive sequencing), a novel approach that employs secretory protein nanocages fused with RNA-binding proteins (RBPs) to capture the RBP-RNA interactome transcriptome in cells. reliably identifies targets canonical RBPs across multiple types. By fusing poly(A)-binding (PABPC1) nanocage, demonstrate can monitor transcriptomic changes response signaling stimuli selectively cell-type-specific transcriptomes mixed populations. Additionally, facilitates dissection domains key amino acid residues critical interactions. We further highlight its utility large-scale screening, offering compelling evidence pathogenicity FMR1 variants. represents transformative advancement biology, biology precision medicine, enabling unprecedented insights into cellular dynamics disease mechanisms.

Язык: Английский

---

Research Progress of Zinc Finger Protein in Gastrointestinal Tumors

Journal of Clinical Personalized Medicine, Год журнала: 2025, Номер 04(02), С. 487 - 494

Опубликована: Янв. 1, 2025

Язык: Английский

---

Environmental Exposure, Epitranscriptomic Perturbations, and Human Diseases

Environmental Science & Technology, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Epitranscriptomics is a rapidly evolving field, and it examines how chemical modifications on RNA regulate gene expression. Increasing lines of evidence support that exposure to various environmental agents can change substantially RNA, thereby perturbing expression contributing disease development in humans. However, the molecular mechanisms through which impairs modification-associated proteins ("reader", "writer", "eraser" or RWE proteins) alters landscape remain poorly understood. Here, we provide our perspectives current knowledge about epitranscriptome, where focus dynamic changes their regulatory elicited by agents. We discuss these epitranscriptomic alterations may contribute human diseases, especially neurodegeneration cancer. also potential technical challenges harnessing as biomarkers for monitoring exposure. Finally, emphasize need integrate multiomics approaches decipher complex interplay between epitranscriptome offer forward-looking viewpoint future research priorities inform public health interventions regulations.

Язык: Английский

---

Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Март 25, 2025

Abstract Background Acute myeloid leukemia (AML) is the most common type of acute leukemia, accounting for 20% cases in children and adolescents. Genome-wide studies have identified genes that are commonly mutated AML, including many epigenetic regulators involved either DNA methylation ( DNMT3A , TET2 IDH1/2 ) or histone post-translational modifications ASXL1 EZH2 MLL1 ). Several cell lines derived from AML patients widely used cancer research. Whether important differences these exist remains poorly characterised. Results Here, we RNA sequencing (RNA-Seq) to contrast transcriptome four AML-derived lines: THP-1, NOMO-1, MOLM-13 bearing initiating t(9;11) translocation, MV4.11 t(4;11) translocation. Gene set enrichment analyses comparison key transcription regulator revealed transcriptome, distinguishing models. Among these, found striking expression clusters located on chromosome 19 encoding Zinc Finger (ZNF) transcriptional repressors. Low ZNF within associated with poor survival patients. Conclusion The present study offers a valuable resource by providing detailed comparative characterisation same subtype as models

Язык: Английский

---

N-6-methyladenosine (m6A) promotes the nuclear retention of mRNAs with intact 5′ splice site motifs

Life Science Alliance, Год журнала: 2024, Номер 8(2), С. e202403142 - e202403142

Опубликована: Дек. 3, 2024

In humans, misprocessed mRNAs containing intact 5′ Splice Site (5′SS) motifs are nuclear retained and targeted for decay by ZFC3H1, a component of the Poly(A) Exosome Targeting complex, U1-70K, U1 snRNP. S. pombe , ZFC3H1 homolog, Red1, binds to YTH domain–containing protein Mmi1 targets certain RNA transcripts foci retention decay. Here we show that YTHDC1 YTHDC2, two domain-containing proteins bind N -6-methyladenosine (m6A) modified RNAs, interact with required 5′SS motifs. Disruption m6A deposition inhibits both these their accumulation in YTHDC1-enriched adjacent speckles. Endogenous RNAs motifs, such as intronic poly-adenylated transcripts, tend be m6A-modified at low levels. Thus, modification acts on conserved quality control mechanism

Язык: Английский

---

A distinct mechanism of RNA recognition by the transcription factor GATA1

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 2, 2024

ABSTRACT Several human transcription factors (TFs) have been reported to directly bind RNA through non-canonical RNA-binding domains; however, most of these TFs remain be further validated as bona fide proteins (RBPs). Our systematic analysis RBP discovery datasets reveals a varied set candidate TF-RBPs that encompass TF families. These RBPs include members the GATA family, which are essential in embryonic development. Investigation features GATA1, major hematopoietic TF, robust non-sequence specific binding RNAs vitro . Moreover, by GATA1 is competitive with DNA binding, occurs shared surface spanning DNA-binding domain and arginine-rich motif (ARM) like domain. We show ARM-like contributes both substantially high-affinity electrostatically plastic recognition, suggesting separable RBD assigned ARM-domain an oversimplification more complex recognition network. biochemical data demonstrate unified integration DNA- surfaces within whereby provides electrostatic for but does not fully dominate GATA1-RNA interactions, may also apply other TF-RBPs. This DNA/RNA activity using overlapping nucleic acid regions points possibility RNA-mediated regulation function during hematopoiesis. study highlights multifunctionality domains supports need characterization predicted such domains.

Язык: Английский

---

The N-terminus of YY1 regulates DNA and RNA binding affinity for both the zinc-fingers and an unexpected nucleic acid binding domain

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 5, 2024

ABSTRACT Transcription factors (TFs) play central roles in dictating cellular identity and function by regulating gene expression programs. Beyond their well-folded DNA binding domains (DBDs) which recognize cognate elements the genome, TFs are enriched for intrinsically disordered regions (IDRs), have a host of proposed functions including facilitating protein-protein interactions, aiding site search, RNA. Defining intrinsic regulatory properties requires further mechanistic investigation. We chose to investigate RNA Yin Yang 1 (YY1), ubiquitously expressed TF directly involved transcriptional activation, repression genome architecture. Through systematic vitro nucleic acid experiments we resolve conflicting literature defining interface YY1, demonstrating that there two within YY1: its canonical 4 zinc finger DBD previously unannotated domain, term REPO-NAB. Furthermore, discover surprising autoinhibitory N-terminus protein imparts on each these domains. Our results provide new example IDR-mediated regulation enables future mechanistically precise functional investigations.

Язык: Английский

---

The RNA Revolution in the Central Molecular Biology Dogma Evolution

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12695 - 12695

Опубликована: Ноя. 26, 2024

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now RNA revolution, propelled by realization that genes determine phenotype beyond foundational central molecular biology dogma, stating inherited linear pieces of DNA transcribed to RNAs and translated into proteins. Crucially, over 95% genome, initially considered junk between genes, encodes essential, functionally diverse non-protein-coding RNAs, raising gene count at least one order magnitude. Most phenotype-determining changes regulatory areas control can directly or indirectly phenotypes regulating protein function, transferring information within organisms, generating DNA. also exhibit high structural, functional, biomolecular interaction plasticity modified via editing, methylation, glycosylation, other mechanisms, which bestow them with intra- extracellular functions without altering underlying is, therefore, currently primary determinant cellular populational functional diversity, disease-linked structural variations, cell function regulation. As demonstrated RNA-based coronavirus vaccines' success, technology is transforming medicine, agriculture, industry, as did advent recombinant 1980s.

Язык: Английский

---