No abstract available.
Animals ; Gonadotropin-Releasing Hormone* ; Mice* ; RNA Precursors*

Precursor messenger RNA (pre-mRNA) splicing is catalyzed by an intricate ribonucleoprotein complex called the spliceosome. Although the spliceosome is considered to be general cell "housekeeping" machinery, mutations in core components of the spliceosome frequently correlate with cell- or tissue-specific phenotypes and diseases. In this review, we expound the links between spliceosome mutations, aberrant splicing, and human cancers. Remarkably, spliceosome-targeted therapies (STTs) have become efficient anti-cancer strategies for cancer patients with splicing defects. We also highlight the links between spliceosome and immune signaling. Recent studies have shown that some spliceosome gene mutations can result in immune dysregulation and notable phenotypes due to mis-splicing of immune-related genes. Furthermore, several core spliceosome components harbor splicing-independent immune functions within the cell, expanding the functional repertoire of these diverse proteins.
Humans ; Neoplasms/metabolism* ; RNA Precursors/metabolism* ; RNA Splicing ; RNA Splicing Factors/metabolism* ; Spliceosomes/metabolism*

Alternative splicing (AS) is an important mechanism of producing transcriptome diversity and microarray techniques are being used increasingly to monitor the splice variants. There exist three types of microarrays interrogating AS events-junction, exon, and tiling arrays. Junction probes have the advantage of monitoring the splice site directly. Johnson et al., performed a genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays (Science 302:2141-2144, 2003), which monitored splicing at every known exon-exon junctions for more than 10,000 multi-exon human genes in 52 tissues and cell lines. Here, we describe an algorithm to deduce the relative concentration of isoforms from the junction array data. Non-negative Matrix Factorization (NMF) is applied to obtain the transcript structure inferred from the expression data. Then we choose the transcript models consistent with the ECgene model of alternative splicing which is based on mRNA and EST alignment. The probe-transcript matrix is constructed using the NMF-consistent ECgene transcripts, and the isoform abundance is deduced from the non-negative least squares (NNLS) fitting of experimental data. Our method can be easily extended to other types of microarrays with exon or junction probes.
Alternative Splicing ; Cell Line ; Exons* ; Humans ; Least-Squares Analysis ; Protein Isoforms ; RNA Precursors ; RNA, Messenger ; Transcriptome

Alternative splicing of pre-mRNA is an important mechanism for regulating gene function at the post-transcription level and for producing proteomic diversity in higher eukaryotes. The alternative splicing is regulated by the interaction between diverse cis-acting elements and trans-acting factors. Alternative splicing events of oncogenes, tumor suppressor genes and metastasis suppressor genes are associated with the initiation and development of human neoplasms. The protein isoforms sourced from alternative splicing take part in regulating the gene transcription, cell cycle, apoptosis of cells, and playing a role in tumor growth. It is possible for molecular therapy to target directly isoforms of protein produced by alternative splicing or to interfere with the process of alternative splicing.
Alternative Splicing ; genetics ; Humans ; Neoplasms ; genetics ; RNA Precursors ; metabolism ; RNA, Neoplasm ; analysis ; Transcription, Genetic

T-cell internal antigen-1 (TIA-1) has roles in regulating alternative pre-mRNA splicing, mRNA translation, and stress granule (SG) formation in human cells. As an evolutionarily conserved response to environmental stress, SGs have been reported in various species. However, SG formation in chicken cells and the role of chicken TIA-1 (cTIA-1) in SG assembly has not been elucidated. In the present study, we cloned cTIA-1 and showed that it facilitates the assembly of canonical SGs in both human and chicken cells. Overexpression of the chicken prion-related domain (cPRD) of cTIA-1 that bore an N-terminal green fluorescent protein (GFP) tag (pntGFP-cPRD) or Flag tag (pFlag-cPRD) induced the production of typical SGs. However, C-terminal GFP-tagged cPRD induced notably large cytoplasmic granules that were devoid of endogenous G3BP1 and remained stable when exposed to cycloheximide, indicating that these were not typical SGs, and that the pntGFP tag influences cPRD localization. Finally, endogenous cTIA-1 was recruited to SGs in chicken cells and tissues under environmental stress. Taken together, our study provide evidence that cTIA-1 has a role in canonical SG formation in chicken cells and tissues. Our results also indicate that cPRD is necessary for SG aggregation.
Chickens ; Clone Cells ; Cycloheximide ; Cytoplasmic Granules ; Humans ; Protein Biosynthesis ; RNA Precursors ; RNA-Binding Proteins ; T-Lymphocytes

Varying length of messenger RNA (mRNA) 3′-untranslated region is generated by alternating the usage of polyadenylation sites during pre-mRNA processing. It is prevalent through all eukaryotes and has emerged as a key mechanism for controlling gene expression. Alternative polyadenylation (APA) plays an important role for cell growth, proliferation, and differentiation. In this review, we discuss the functions of APA related with various physiological conditions including cellular metabolism, mRNA processing, and protein diversity in a variety of disease models. We also discuss the molecular mechanisms underlying APA regulation, such as variations in the concentration of mRNA processing factors and RNA-binding proteins, as well as global transcriptome changes under cellular signaling pathway.
Eukaryota ; Gene Expression ; Humans* ; Metabolism ; Polyadenylation* ; RNA Precursors ; RNA, Messenger ; RNA-Binding Proteins ; TOR Serine-Threonine Kinases ; Transcriptome

Aged ; Female ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; RNA Precursors

Treacher Collins syndrome (TCS) is the most common and well known mandibulofacial dysostosis with characteristic clinical features including downward slanting of palpebral fissures, coloboma of the lower eyelid, hypoplastic zygomatic arches, micrognathia, macrostomia, microtia, and other deformities of the ears. TCS is caused by mutations in at least 3 genes involved in pre-rRNA transcription: TCOF1, POLR1D and POLR1C. We experienced a 1-day-old female infant with characteristic clinical features of TCS. A novel, heterozygotic mutation within the TCOF1 gene (c.3874_3875insG, p.Ala1292Glyfs*30) was identified to cause a premature stop codon.
Codon, Nonsense ; Coloboma ; Congenital Abnormalities ; Ear ; Exons* ; Eyelids ; Female ; Humans ; Infant ; Infant, Newborn* ; Macrostomia ; Mandibulofacial Dysostosis* ; RNA Precursors ; Zygoma

BACKGROUND: Through differentiation processes, keratinocytes provide a physical barrier to our bodies and control skin features such as moisturization, wrinkles and pigmentation. Keratinocyte differentiation is disturbed in several skin diseases such as psoriasis and atopic dermatitis. OBJECTIVE: The aim of this study is to evaluate the keratinocyte differentiation-enhancing effect of rose absolute oil (RAO). METHODS: Primary cultured human normal keratinocytes were treated with RAO, and differentiation then checked by the expression of marker genes. RESULTS: RAO did not induce cytotoxicity on cultured keratinocytes at a dose of 10microM. The level of involucrin, an early marker for keratinocyte differentiation, was significantly increased by RAO. Concomitantly, RAO increased involucrin promoter activity, indicating that RAO increased involucrin gene expression at the mRNA level. Furthermore, RAO increased the level of filaggrin in cultured keratinocytes, and in the granular layer of mouse skin. In line with these results, RAO decreased the proliferation of keratinocytes cultured in vitro. When RAO was applied topically on the tape-stripped mouse skins, it accelerated the recovery of disturbed barrier function. CONCLUSION: These results suggest that RAO may be applicable for the control of skin texture and keratinocyte differentiation-related skin diseases.
Animals ; Dermatitis, Atopic ; Gene Expression ; Humans ; Intermediate Filament Proteins ; Keratinocytes ; Mice ; Pigmentation ; Protein Precursors ; Psoriasis ; RNA, Messenger ; Skin ; Skin Diseases

OBJECTIVE: The aim of this study was to investigate the gene expression profiles using GeneFishing(TM) DEG kit in Korean women with cervical squamous cell carcinoma. METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, St. Mary's hodpital. In this study, we used a common reference that was mixed with an equal amount of RNA extracted from non-cervical cancer patients. The profiles of expression genes between cervical normal and squamous cell carcinoma tissue were identified using GeneFishing(TM) DEG Kit and screened by BLAST search. RESULTS: Almost 100 differential expressed genes were identified in universal control and cervical squamous cell carcinoma, 53 of differential expressed genes, up-regulated expression of 32 and 21 down-regulated expression was sequenced. Up-regulated genes were calcylin, calgranulin A, TRK oncogene, HLC5, fibrillarin, collagene type I alpha1 etc. and down-regulated genes were galectin 1, PRP8 pre-mRNA precessing factor 8 homology, clusterin etc. CONCLUSION: We identified gene expression profile in cervical squamous cell carcinoma using GeneFishing(TM) Kit in Korean women. The functional genomics of these genes should be further studied.
Biopsy ; Calgranulin A ; Carcinoma, Squamous Cell* ; Clusterin ; Collagen ; Female ; Galectin 1 ; Gene Expression* ; Genomics ; Gynecology ; Humans ; Obstetrics ; Oncogenes ; Polymerase Chain Reaction* ; RNA ; RNA Precursors ; Transcriptome ; Uterine Cervical Neoplasms