BiFC and FACS-based CRISPR screening revealed that QKI promotes PABPN1 LLPS in colorectal cancer cells.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS).

E3 ligase SYVN1-mediated polyubiquitination of CPSF6 promotes alternative polyadenylation and antivirus effects of macrophages.

Transcriptome-wide alternative polyadenylation (APA) is involved in both innate and adaptive immune responses of immune cells. Downregulation of the CPSF6 protein, one of the 3' end-processing factors, mediates APA in macrophages with responses to virus infection and plays an important role in its anti-virus effect. However, the signaling pathway and molecular mechanism underlying the downregulation of the CPSF6 protein remain elusive.

Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus.

Objective: To assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT).

Materials And Methods: This study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed.

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1.

Generally shortened 3' UTR due to alternative polyadenylation (APA) is widely observed in cancer, but its regulation mechanisms for cancer are not well characterized. Here, with profiling of APA in colorectal cancer tissues and poly(A) signal editing, we firstly identified that the shortened 3' UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration. We found that liquid-liquid phase separation (LLPS) of PABPN1 is reduced albeit with higher expression in cancer, and the reduction of LLPS leads to the shortened 3' UTR of CTNNBIP1 and promotes cell proliferation and migration.

Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown.

Assessment of Ki-67 proliferation index in prognosis prediction in patients with nonmetastatic clear cell renal cell carcinoma and tumor thrombus.

Purpose: To determine the optimal cut-off value of Ki-67 for predicting the survival of patients with clear cell renal cell carcinoma (ccRCC) and tumor thrombus and to explore the correlation between Ki-67 expression and pathological features.

Patients And Methods: We retrospectively analyzed Ki-67 immunohistochemical staining of ccRCC and tumor thrombus resected from February 2006 to February 2022. The survival rate was evaluated using the Kaplan-Meier method.

CPSF6 regulates alternative polyadenylation and proliferation of cancer cells through phase separation.

Cancer cells usually exhibit shortened 3' untranslated regions (UTRs) due to alternative polyadenylation (APA) to promote cell proliferation and migration. Upregulated CPSF6 leads to a systematic prolongation of 3' UTRs, but CPSF6 expression in tumors is typically higher than that in healthy tissues. This contradictory observation suggests that it is necessary to investigate the underlying mechanism by which CPSF6 regulates APA switching in cancer.

Objective Value of the Apparent Diffusion Coefficient (ADC) Map from Ultrahigh b-value Diffusion-weighted Imaging (DWI) in 3T MRI could be a Non-invasive Specific Biomarker for Prostate Cancer.

Objective: This article aims to explore the ADC value of ultrahigh b-value DWI and the diagnostic cutoff point in prostate cancer.

Methods: A total of 78 patients were included in this study. T2 weighted imaging (T2WI), conventional diffusion-weighted imaging (DWI) (1000 s/mm2), and DWI with ultrahigh b-values of 2000 s/mm2 and 3000 s/mm2 were performed in each patient.

Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging and Venous Tumor Thrombus Consistency in Renal Cell Carcinoma.

Background: Venous tumor thrombus (VTT) consistency of renal cell carcinoma (RCC) is an important consideration in nephrectomy plus thrombectomy. However, evaluation of VTT consistency through preoperative MR imaging is lacking.

Purpose: To evaluate VTT consistency of RCC through intravoxel incoherent motion-diffusion weighted imaging (IVIM-DWI) derived parameters (D , D , f, and ADC) and the apparent diffusion coefficient (ADC) value.

Nuclear m A reader YTHDC1 suppresses proximal alternative polyadenylation sites by interfering with the 3' processing machinery.

N6-methyladenosine (m A) and alternative polyadenylation (APA) are important regulators of gene expression in eukaryotes. Recently, it was found that m A is closely related to APA. However, the molecular mechanism of this new APA regulation remains elusive.

U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3' end processing core factors.

In eukaryotic cells, both alternative splicing and alternative polyadenylation (APA) play essential roles in the gene regulation network. U1 small ribonucleoprotein particle (U1 snRNP) is a major component of spliceosome, and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3' end processing factors. However, here we show that both knockdown and overexpression of SNRPA, SNRPC, SNRNP70, and SNRPD2, the U1 snRNP proteins, promote the usage of proximal APA sites at the transcriptome level.

Identifying novel conopepetides from the venom ducts of Conus litteratus through integrating transcriptomics and proteomics.

The venom ducts of marine cone snails secrete highly complex mixtures of cysteine-rich active peptides, which are generally known as conotoxins or conopeptides and provide a potential fertile resource for pharmacological neuroscience research and the discovery of new drugs. Previous studies have devoted substantial effort to the identification of novel conopeptides, and the 109 cone snail species have yielded 7000 known conopeptides to date. Here, we used de novo deep transcriptome sequencing analyses combined with traditional Sanger sequencing and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) to identify 30 distinct conopeptide precursors.

Crosstalk between alternative polyadenylation and miRNAs in the regulation of protein translational efficiency.

3' UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency, and subcellular localization. For a given gene, 3' UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3' UTRs alter gene function remain unclear.

Cell Cycle Regulation by Alternative Polyadenylation of CCND1.

Global shortening of 3'UTRs by alternative polyadenylation (APA) has been observed in cancer cells. However, the role of APA in cancer remains unknown. CCND1 is a proto-oncogene that regulates progression through the G1-S phase of the cell cycle; moreover, it has been observed to be switching to proximal APA sites in cancer cells.

Small Nuclear Ribonucleoprotein Polypeptide A-Mediated Alternative Polyadenylation of STAT5B during Th1 Cell Differentiation.

T cells are activated and differentiated into Th cells depending on the rapid and accurate changes in the cell transcriptome. In addition to changes in mRNA expression, the sequences of many transcripts are altered by alternative splicing and alternative polyadenylation (APA). We profiled the APA sites of human CD4 T cell subsets with high-throughput sequencing and found that Th1 cells harbored more genes with shorter tandem 3' untranslated regions (UTRs) than did naive T cells.

The role of alternative polyadenylation in the antiviral innate immune response.

Alternative polyadenylation (APA) is an important regulatory mechanism of gene functions in many biological processes. However, the extent of 3' UTR variation and the function of APA during the innate antiviral immune response are unclear. Here, we show genome-wide poly(A) sites switch and average 3' UTR length shortens gradually in response to vesicular stomatitis virus (VSV) infection in macrophages.

IVT-SAPAS: Low-Input and Rapid Method for Sequencing Alternative Polyadenylation Sites.

Gene transcribing with alternative polyadenylation (APA) sites leads to mRNA isoforms, which may encode different proteins or harbor different 3'UTRs. APA plays an important role in regulating gene expression network among various physiological processes, such as development, immune responses and cancer. Several methods of library construction for APA study have been developed to apply high-throughput sequencing.

[Association of the H770H of PR gene polymorphism with susceptibility to endometriosis].

Objective: To investigate the association of PR gene exon 5 region H770H (rs1042839) single nucleotide polymorphism (SNP) with the genetic susceptibility to endometriosis (EM) in southern Han Chinese women.

Methods: Totally 431 EM patients and 499 non-EM women were collected and separated into EM group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in EM and control groups to evaluate the association of these SNP with the susceptibility to EM by using a fluorescent quantitative PCR-based high resolution melting (HRM) method.

Evaluation of two statistical methods provides insights into the complex patterns of alternative polyadenylation site switching.

Switching between different alternative polyadenylation (APA) sites plays an important role in the fine tuning of gene expression. New technologies for the execution of 3'-end enriched RNA-seq allow genome-wide detection of the genes that exhibit significant APA site switching between different samples. Here, we show that the independence test gives better results than the linear trend test in detecting APA site-switching events.

The genetic basis of population fecundity prediction across multiple field populations of Nilaparvata lugens.

Identifying the molecular markers for complex quantitative traits in natural populations promises to provide novel insight into genetic mechanisms of adaptation and to aid in forecasting population dynamics. In this study, we investigated single nucleotide polymorphisms (SNPs) using candidate gene approach from high- and low-fecundity populations of the brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) divergently selected for fecundity. We also tested whether the population fecundity can be predicted by a few SNPs.

Decelerated genome evolution in modern vertebrates revealed by analysis of multiple lancelet genomes.

Vertebrates diverged from other chordates ~500 Myr ago and experienced successful innovations and adaptations, but the genomic basis underlying vertebrate origins are not fully understood. Here we suggest, through comparison with multiple lancelet (amphioxus) genomes, that ancient vertebrates experienced high rates of protein evolution, genome rearrangement and domain shuffling and that these rates greatly slowed down after the divergence of jawed and jawless vertebrates. Compared with lancelets, modern vertebrates retain, at least relatively, less protein diversity, fewer nucleotide polymorphisms, domain combinations and conserved non-coding elements (CNE).

APASdb: a database describing alternative poly(A) sites and selection of heterogeneous cleavage sites downstream of poly(A) signals.

Increasing amounts of genes have been shown to utilize alternative polyadenylation (APA) 3'-processing sites depending on the cell and tissue type and/or physiological and pathological conditions at the time of processing, and the construction of genome-wide database regarding APA is urgently needed for better understanding poly(A) site selection and APA-directed gene expression regulation for a given biology. Here we present a web-accessible database, named APASdb (http://mosas.sysu.

Polymorphism of DEFA in Chinese Han population with IgA nephropathy.

Our recent genome-wide association study (GWAS) had discovered a new locus at 8p23 (rs2738048) associated with IgA nephropathy (IgAN) in Chinese Han patients, implicating the DEFA gene family within this locus as susceptibility genes. However, it is still unknown whether there are additional variations within these genes associated with the disease susceptibility. The aim of this study is to investigate the polymorphisms of DEFA genes in the susceptibility to IgAN and explore possible disease mechanisms.

Tandem alternative polyadenylation events of genes in non-eosinophilic nasal polyp tissue identified by high-throughput sequencing analysis.

Nasal polyps (NP) is highly associated with the disorder of immune cells. Alternative polyadenylation (APA) produces mRNA isoforms with different length of 3'‑untranslated region (UTR) and regulates gene expression. It has been proven that this APA-mediated regulation of 3'UTR length is an immune-associated phenomenon.

The effects of both single-locus and multi-locus interaction on the clinical manifestations of IgA nephropathy in Southern Han Chinese.

Background: Immunoglobulin A nephropathy (IgAN) is one of the most common types of glomerulonephritis throughout the world. It is considered to be a complex disease, to which both genetic and environmental factors contribute. Our previous study has shown a potential interaction of C1GALT1-330G/T and IL5RA31 + 197A/G on the susceptibility of IgAN in Southern Han Chinese.