Insulin-like growth factor-1 (IGF-1) has become an interesting potential therapeutic target for muscle wasting disorders, since it is known to modulat…

Activity-dependent gene expression in neurons is well established, yet few studies have examined activity-dependent alternative splicing. Alternative splicing regulates >95% of genes and is essential…

PubMed link

Alternative splicing is essential for plants, enabling a single gene to produce multiple transcript variants to boost functional diversity and fine-tune responses to environmental and developmental ...

The molecular characterization of the activity of the RNA-binding protein LSM12 and its interplay with SAMD4A reveals that LSM12 promotes lung squamous cell carcinoma progression by regulating alterna...

Papillary thyroid cancer (PTC) is an ever-increasing cancer type worldwide, and greatly decreases the life quality and affects survival time of patients during its development and progression, but the underlying mechanisms and key factors for PTC progression are not clear. Recent studies demonstrated the potassium channel protein SK4 participates in the progression of many cancers, while it lacks the molecular mechanism study for SK4 function. In this study, we performed functional and molecular explorations for SK4 by overexpressing its level in thyroid cancer BHT101 cells. Cellular proliferation and invasion experiments were performed to assess the influences of SK4 on cell behaviors. Further, whole transcriptome sequencing (RNA-seq) analysis helped us systematically investigated the targets of SK4, including differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs), and validated several related DEGs and RASEs by RT-qPCR experiment. In thyroid cancer patients, SK4 expression was completely lost in normal tissues and significantly increased in every stage of tumor tissues compared with normal tissues, which probably results from the low DNA methylation level at its promoter region. Consistent with previous study, SK4 overexpression (SK4-OE) promoted proliferation and invasion ability of BHT10 cells compared with negative control (NC). By analyzing the RNA-seq data, we detected dozens of DEGs and found that up DEGs were enriched in negative regulation of apoptotic progress, including VTCN1, MSX1, FATE1, TEK, and PRAMEF2. More importantly, we found SK4-OE globally changed the alternative splicing (AS) pattern and identified 1,639 RASEs. The genes of RASEs were enriched in DNA damage/repair, viral process, translation, and mRNA splicing pathways, which were tightly associated with the pathogenesis and progression of cancers. The splicing regulatory genes from regulated alternative splicing genes (RASGs) could partly explain the reason of global AS dysregulation by SK4-OE in BHT101 cells. Finally, we found the expression of VTCN1, EDN1, SLC29A4, RP11-473M20.16, and CH507-513H4.4 were validated by RT-qPCR, as well as the AS pattern of TMEM116. In summary, we highlight that SK4-regulated AS pattern probably is a novel regulatory mechanism for SK4 in PTC. The identified DEGs and RASEs, as well as SK4 itself, could be used as potential therapeutic targets for PTC treatment in future.

Recent studies capitalizing on the newly complete nanometer-resolution Drosophila larval connectome have made significant advances in identifying the structu...

Khyzha et al. developed SLAM-RT&Tag, a kinetic labeling strategy for profiling RNA dynamics within nuclear compartments. Applied to Polycomb domains and nuclear speckles, they identified compartment-s...

Nostramo et al. demonstrate that free introns of tRNAs (fitRNAs) are a previously unknown class of small noncoding regulatory RNAs that bind to complementary sequences on mRNA ORFs, leading to decay. ...

Wu et al. reveal that the splicing factor U2AF2 binds chromatin independently of RNA to guide accurate exon selection during transcription. Their findings uncover a chromatin-based mechanism that enhances splicing efficiency and ensures proper expression of genes essential for RNA processing.

The RNA-binding protein Sex-lethal (Sxl) is classically known as a master regulator of sex determination and mRNA splicing in Drosophila melanogaster. However, this role is not conserved across specie...

Common oncogenic RNA splicing factor mutations in myeloid malignancies generate recurrent splicing-derived neoantigens, which can be selectively targeted using a T cell receptor-based approach.

Kim et al. uncover a role for U1 snRNP in regulating internal promoter activity. Beyond its canonical role in splicing, U1 snRNP suppresses premature polyadenylation, enabling upstream transcription t...

Cells sense mechanical cues and convert them into biochemical responses to regulate biological processes such as embryonic development, aging, cellular homeostasis, and disease progression. In this st...

Your access to the NCBI website at www.ncbi.nlm.nih.gov has been temporarily blocked due to a possible misuse/abuse situation involving your site. This is not an indication of a security issue such as a virus or attack. It could be something as simple as a run away script or learning how to better use E-utilities, http://www.ncbi.nlm.nih.gov/books/NBK25497/, for more efficient work such that your work does not impact the ability of other researchers to also use our site. To restore access and understand how to better interact with our site to avoid this in the future, please have your system administrator contact info@ncbi.nlm.nih.gov.

Alterations in pre-mRNA splicing play an important role in disease pathophysiology. However, the rol

The assembly and specification of synapses in the brain is incompletely understood. Latrophilin-3, a

The greater amberjack (Seriola dumerili) is a kind of widely distributed and economically important

Neuro-Oncological Ventral Antigen 1 (NOVA1) is best known for its role in mediating an alternative s

Our researchers are combining single cell approaches with long read sequencing technologies, unearthing data that reveals the scale and impact of cellular diversity.

This work shows that hnRNPC recognizes and binds directly to key meiosis-related genes and works with HuR to regulate alternative splicing of its target genes, ensuring the normal production and proper function of essential meiotic transcripts required for meiotic initiation and progression during the first wave of spermatogenesis. Abstract N6-methyladenosine (m6A) and its reader proteins are involved in pre-mRNA processing and play a variety of roles in numerous biological processes. However, much remains to be understood about the regulation of m6A and the function of its specific readers during meiotic processes. Here, this study shows that the potential m6A reader protein hnRNPC is essential for both male and female meiosis in mice. Germ cell-specific knockout of Hnrnpc causes meiotic arrest at pachynema in male mice. Specifically, hnRNPC-deficient males show abnormal meiosis initiation and defective meiotic progression, ultimately leading to meiotic arrest at the pachytene stage. Interestingly, hnRNPC-null females show similar meiotic defects to males. Mechanistically, this study discovers that in male germ cells, hnRNPC works with HuR to directly bind and modulate alternative splicing of meiotic-related genes (e.g., Sycp1 , Brca1 , and Smc5 ) in an m6A-dependent manner during spermatogenesis. Collectively, these findings reveal hnRNPC as a critical factor for meiosis and contribute to a mechanistic understanding of the hnRNPC-HuR interaction in alternative splicing of mRNAs during germ cell development.

The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor …