JOURNAL OF MOLECULAR BIOLOGY分子生物学杂志
JOURNAL OF MOLECULAR BIOLOGY(英文缩写 J MOL BIOL),ISSN 0022-2836,eISSN 1089-8638,中文译名:分子生物学杂志 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 6.151 | Q1 |
| 2022 | 5.600 | Q1 |
| 2023 | 4.700 | Q1 |
| 2024 | 4.500 | Q2 |
| 2025 | 4.700 | Q2 |
JOURNAL OF MOLECULAR BIOLOGY 最新收录文献
-
2. Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.
PMID:日期:2026-10-15The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.
-
3. DIS3L2 and Nonsense-mediated Decay: United to Degrade.
PMID:日期:2026-10-15Nonsense-mediated decay (NMD) is a vital RNA surveillance mechanism in eukaryotic cells that ensures mRNA quality and regulates gene expression. NMD targets mRNAs with premature translation-termination codons to prevent the production of potentially harmful truncated proteins. But NMD is also involved in modulating the expression of physiological mRNAs to maintain cellular homeostasis. This NMD function is particularly relevant to calibrate the cellular transcriptome in response to environmental signals and stress. Its conservation across eukaryotes highlights its essential role. When active, NMD promotes mRNA degradation involving exoribonucleases such as XRN1 (5'-3') and the exosome (3'-5'). DIS3L2, an exosome-independent exonuclease that primarily targets substrates marked by the non-templated addition of uridine residues to the 3' end of RNA molecules by terminal uridylyl transferases, can also degrade some NMD substrates, especially those that underwent 3' end uridylation. This review explores DIS3L2's interaction with the NMD pathway (DIS3L2/NMD pathway) and the human disorders associated with a dysfunctional DIS3L2/NMD pathway. A better understanding of the interplay between NMD and DIS3L2 will certainly allow the development of novel treatments for disorders associated with an affected DIS3L2/NMD pathway.
-
4. UPF3A and UPF3B Shape the Transcriptome Cooperatively Yet Oppose Cell Function.
PMID:日期:2026-10-15The nonsense mediated mRNA decay (NMD) pathway is a major regulator of gene expression that is essential for normal development and physiology. NMD is orchestrated by the activities of three core NMD proteins UPF1, UPF2 and UPF3B. While complete loss of function of UPF1 or UPF2 is embryonic lethal, loss of function of UPF3B is viable. In the absence of UPF3B, NMD is thought to be rescued by the redundant functions of the UPF3B paralog UPF3A. However, full redundancy of these paralogs is challenged by the embryonic lethality of UPF3A loss of function, and neurodevelopmental phenotypes observed in humans and mice lacking UPF3B. To compare the functions of the UPF3 paralogs we generated L-cell lines with different relative UPF3A and UPF3B abundances via knockdown and/or overexpression. RNA sequencing of UPF3 manipulated L-cells highlighted a major overlap of transcriptome changes following loss of UPF3A or UPF3B, yet overexpression of UPF3A could not rescue changes caused by loss of UPF3B. This suggested both genes are required for NMD in L-cells in a non-redundant manner. However, despite the general similarity of transcriptome changes, loss of UPF3B caused hyper-proliferation, while loss of UPF3A caused a hypo-proliferation of L-cells, and was associated with discordant activation of mTOR signalling. We observe similar opposing impacts of UPF3 manipulation in the context of neural progenitor cell proliferation and differentiation, and neuronal axon growth. These data suggest that while UPF3A and UPF3B generally act cooperatively to tune the transcriptome, their private or discordant functions can drive major biological impact.
-
5. Antibody-secreting Cells Integrate Efficient NMD With Non‑canonical UPR Signaling to Maintain Proteostasis and Support Massive Immunoglobulin Synthesis.
PMID:日期:2026-10-15Plasma cells are terminally differentiated B lymphocytes specialized in the high‑level production and secretion of antibodies. To accommodate the persistent load imposed on the endoplasmic reticulum (ER), plasma cell differentiation engages a sustained unfolded protein response (UPR). Although the UPR is known to attenuate nonsense‑mediated mRNA decay (NMD) in many cell types, the interplay between these pathways during plasma cell differentiation remains poorly defined. We show that NMD is rapidly enhanced during B cell activation and remains high in antibody‑secreting cells (ASCs), even as these cells activate the UPR. Using mouse models enabling in vivo monitoring of NMD under enforced ER stress, we identify limited activation of the PERK-eIF2α axis as a key determinant preserving NMD activity while supporting robust immunoglobulin synthesis. Supporting a key role for NMD in B cell activation and ASC differentiation, antisense oligonucleotide‑mediated knockdown of Upf1 severely compromised cell viability. Moreover, we provide evidence for efficient degradation of endogenous NMD substrates in myeloma cells, suggesting a functional role for NMD in multiple myeloma. Taken together, these findings reveal an integrated protein quality‑control network in ASCs that relies on the coordinated action of NMD and non‑canonical UPR signaling to maintain proteostasis and support massive immunoglobulin synthesis.
-
6. UPF1 at Work: Structural and Mechanistic Insights Into a Master Regulator of Nonsense-Mediated mRNA Decay.
PMID:日期:2026-10-15RNA helicases are central architects of ribonucleoprotein (RNP) organization, coupling nucleoside triphosphate hydrolysis to RNA binding to unwind duplexes, translocate along nucleic acids, displace RNA-binding proteins, and remodel RNP assemblies. Among them, UPF1 (UP-Frameshift 1) is a highly conserved superfamily 1 (SF1) helicase and the pivotal effector of nonsense-mediated mRNA decay (NMD). UPF1 harbors the canonical helicase core motifs required for ATP binding and hydrolysis, RNA interaction, and chemo-mechanical coupling, as well as regulatory domains that fine-tune its catalytic activity and protein-protein interactions. UPF1 displays remarkable enzymatic versatility, acting as an RNA translocase, helicase and RNPase. Its capacity to coordinate these distinct but interconnected activities enables dynamic remodeling of messenger RNPs and positions UPF1 as a multifunctional regulator of RNA fate during NMD. In this review, we integrate current structural and mechanistic insights into UPF1 function and propose a unifying framework that links its biochemical properties to its diverse cellular roles, aiming to reconcile the existing models that describe its mechanism of action.
-
7. A Conserved 3'UTR Stem-loop Directs UPF1/eIF4AIII-Dependent Regulation of GABARAPL1 mRNA.
PMID:日期:2026-10-15RNA-binding proteins (RBP) interact with mRNA untranslated regions containing cis-regulatory elements to govern mRNA localization, stability, and translational efficiency. Among these trans-regulatory factors, RNA helicase UPF1 is a central factor which play a role in multiple mRNA decay pathways, including nonsense-mediated mRNA decay (NMD). NMD is triggered when an exon-junction complex (EJC) is located downstream of a premature termination codon. However, in some cases, NMD can be activated in an EJC-independent manner through mechanisms involving the 3'UTR. In the present study, we focused on the GABARAPL1 3'UTR, as previous studies had shown that this region plays a key role in NMD targeting, although the underlying molecular mechanism had not yet been elucidated. Unlike canonical NMD targets such as SC35, we found that the chemical inhibition of eIF4AIII helicase activity did not affect GABARAPL1 transcript levels, indicating that this transcript is regulated through its 3'UTR via an EJC-independent mechanism. We therefore investigated the potential presence of cis-regulatory element within the 3'UTR of GABARAPL1 which can regulate mRNA and protein levels in a UPF1-dependent manner. Furthermore, we identified a conserved RNA region spanning nucleotides 364-421 involved in GABARAPL1 targeting and used biochemical analysis to demonstrate the direct binding of UPF1 and eIF4AIII to this RNA region, to analyse its secondary structure in solution, and to map the protein-binding sites. By complementing these approaches with molecular modelling, we showed that this stem-loop adopts a stable global fold but a local flexibility and dynamic behaviour properties. Together, our results support the role of UPF1 and eIF4AIII as specific regulators of GABARAPL1 transcript and reveal a novel RNA regulatory element within its 3'UTR, which provides a completely unexpected binding site for these factors.
-
8. The Role of Nonsense-mediated mRNA Decay in Aging.
PMID:日期:2026-10-15Aging is a complex biological process that gradually increases vulnerability to death and susceptibility to age-related diseases. Emerging evidence indicates that nonsense-mediated mRNA decay (NMD), a conserved RNA surveillance pathway in eukaryotes, plays a crucial role in the regulation of aging and longevity. In this manuscript, we discuss the role of key NMD factors in aging at the cellular and organismal levels. We highlight the age-related decline in NMD activity in various organisms, which may increase the production of truncated proteins. In addition, we discuss how NMD contributes to longevity and the prevention of cellular senescence. Our review provides valuable information on the molecular mechanisms by which NMD regulates aging, and enhances our understanding of how mRNA quality control, especially NMD, can be utilized for contributing to healthy longevity in humans.
-
9. Translatable Circular RNAs are Degraded Via Nonsense-mediated mRNA Decay.
PMID:日期:2026-10-15Endogenous circular RNAs (circRNAs) are predominantly generated by a back-splicing process. Due to their lacking 5' and 3' termini, circRNA degradation is exclusively dependent on endoribonucleolytic cleavage. In addition, translation occurring on circRNAs depends solely on internal ribosome entry site (IRES) or IRES-like features, such as an exon junction complex (EJC) deposited after back-splicing. However, the potential relationship between the translatability and stability of circRNAs has yet to be explored. Here, we demonstrate that translatable circRNAs can be subject to canonical EJC-dependent nonsense-mediated mRNA decay (NMD), a well-known mRNA surveillance mechanism, as long as circRNAs contain EJC(s) downstream of a translation termination codon. We find that the NMD of translatable circRNAs involves UPF1 and the NMD-specific endoribonuclease SMG6. This distinct pathway is termed NMD-like circRNA decay (NCD). The differences in factor requirements between canonical EJC-dependent NMD and NCD lead to variations in RNA regulation under cellular stress conditions. Our observations provide an additional layer in the molecular regulation of circRNA dynamics.
-
10. Regulation of Eukaryotic Gene Expression Through Functional Coupling Between Alternative Splicing and Nonsense-mediated Decay.
PMID:日期:2026-10-15Alternative pre-mRNA splicing (AS) and nonsense-mediated decay (NMD) are key RNA-based regulatory mechanisms in eukaryotic cells. Although NMD was initially identified as a quality-control pathway targeting aberrant transcripts, increasing evidence indicates that it frequently operates in concert with genetically programmed AS to regulate the expression output of protein-coding genes. Here, we describe AS-NMD mechanisms, highlighting their diverse functions across biological contexts. These include roles in maintaining cellular homeostasis, preventing premature expression of differentiation-specific genes, sharpening gene expression dynamics during development, and fine-tuning responses to physiological cues. We additionally summarize experimental approaches used to study AS-NMD and discuss possible evolutionary mechanisms underlying the acquisition of new regulatory AS-NMD events and their integration into gene regulatory networks. Overall, this review provides a unified perspective on AS-NMD as a widespread, multifaceted, and evolutionarily dynamic regulator of gene expression at the post-transcriptional level.