- Browse by Subject
Browsing by Subject "Base Sequence"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
Item Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient(Oxford Academic, 1996-04) Sun, Yongming; Nicholls, Robert D.; Butler, Merlin G.; Saitoh, Shinji; Hainline, Bryan E.; Palmer, Catherine G.; Medical and Molecular Genetics, School of MedicineA patient with Prader-Willi syndrome (PWS) was found to carry a de novo balanced reciprocal translocation, t(15;19)(q12;q13.41), which disrupted the small nuclear ribonucleoprotein N (SNRPN) locus. The translocation chromosome 15 was found to be paternal in origin. Uniparental disomy and abnormal DNA methylation were ruled out. The translocation breakpoint was found to have occurred between exon 0 (second exon) and 1 (third exon) of the SNRPN locus outside of the SmN open reading frame (ORF), which is intact. The transcriptional activities of ZNF127, IPW, PAR-1, and PAR-5 were detected with RT-PCR from fibroblasts of the patient, suggesting that these genes may not play a significant role in the PWS phenotype in this patient. Transcription from the first two exons and last seven exons of the SNRPN gene was also detected with RT-PCR; however, the complete mRNA (10 exons) was not detected. Thus, the PWS phenotype in the patient is likely to be the result of disruption of the SNRPN locus.Item HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo(Cold Spring Harbor Laboratory Press, 2018-05) Howard, Jonathan M.; Lin, Hai; Wallace, Andrew J.; Kim, Garam; Draper, Jolene M.; Haeussler, Maximilian; Katzman, Sol; Toloue, Masoud; Liu, Yunlong; Sanford, Jeremy R.; Medical and Molecular Genetics, School of MedicineAlternative pre-mRNA splicing plays a major role in expanding the transcript output of human genes. This process is regulated, in part, by the interplay of trans-acting RNA binding proteins (RBPs) with myriad cis-regulatory elements scattered throughout pre-mRNAs. These molecular recognition events are critical for defining the protein-coding sequences (exons) within pre-mRNAs and directing spliceosome assembly on noncoding regions (introns). One of the earliest events in this process is recognition of the 3' splice site (3'ss) by U2 small nuclear RNA auxiliary factor 2 (U2AF2). Splicing regulators, such as the heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), influence spliceosome assembly both in vitro and in vivo, but their mechanisms of action remain poorly described on a global scale. HNRNPA1 also promotes proofreading of 3'ss sequences though a direct interaction with the U2AF heterodimer. To determine how HNRNPA1 regulates U2AF-RNA interactions in vivo, we analyzed U2AF2 RNA binding specificity using individual-nucleotide resolution crosslinking immunoprecipitation (iCLIP) in control and HNRNPA1 overexpression cells. We observed changes in the distribution of U2AF2 crosslinking sites relative to the 3'ss of alternative cassette exons but not constitutive exons upon HNRNPA1 overexpression. A subset of these events shows a concomitant increase of U2AF2 crosslinking at distal intronic regions, suggesting a shift of U2AF2 to "decoy" binding sites. Of the many noncanonical U2AF2 binding sites, Alu-derived RNA sequences represented one of the most abundant classes of HNRNPA1-dependent decoys. We propose that one way HNRNPA1 regulates exon definition is to modulate the interaction of U2AF2 with decoy or bona fide 3'ss.Item [Letter to the editor] PCR prescreen for genotyping the Ts65Dn mouse model of Down syndrome(Future Medicine, 2018-04-03) Lorenzi, Hernan; Duvall, Nichole; Cherry, Sheila M.; Reeves, Roger H.; Roper, Randall J.; Biology, School of ScienceItem A mathematical model of bimodal epigenetic control of miR-193a in ovarian cancer stem cells(PLoS, 2014-12-29) Cheng, Frank H.C.; Aguda, Baltazar; Tsai, Je-Chiang; Kochanczyk, Marek; Lin, Jora M.J.; Chen, Gary C.W.; Lai, Hung-Cheng; Nephew, Kenneth P.; Hwang, Tzy-Wei; Chan, Michael W.Y.; Department of Cellular and Integrative Physiology, IU School of MedicineAccumulating data indicate that cancer stem cells contribute to tumor chemoresistance and their persistence alters clinical outcome. Our previous study has shown that ovarian cancer may be initiated by ovarian cancer initiating cells (OCIC) characterized by surface antigen CD44 and c-KIT (CD117). It has been experimentally demonstrated that a microRNA, namely miR-193a, targets c-KIT mRNA for degradation and could play a crucial role in ovarian cancer development. How miR-193a is regulated is poorly understood and the emerging picture is complex. To unravel this complexity, we propose a mathematical model to explore how estrogen-mediated up-regulation of another target of miR-193a, namely E2F6, can attenuate the function of miR-193a in two ways, one through a competition of E2F6 and c-KIT transcripts for miR-193a, and second by binding of E2F6 protein, in association with a polycomb complex, to the promoter of miR-193a to down-regulate its transcription. Our model predicts that this bimodal control increases the expression of c-KIT and that the second mode of epigenetic regulation is required to generate a switching behavior in c-KIT and E2F6 expressions. Additional analysis of the TCGA ovarian cancer dataset demonstrates that ovarian cancer patients with low expression of EZH2, a polycomb-group family protein, show positive correlation between E2F6 and c-KIT. We conjecture that a simultaneous EZH2 inhibition and anti-estrogen therapy can constitute an effective combined therapeutic strategy against ovarian cancer.Item Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.(ASBMB, 2004-03-19) Laudes, Matthias; Christodoulides, Constantinos; Sewter, Ciaran; Rochford, Justin J.; Considine, Robert V.; Sethi, Jaswinder K.; Vidal-Puig, Antonio; O’Rahilly, Stephen; Department of Medicine, IU School of MedicinePoxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2-4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation.