Dataset Information

Fixed differences in the 3'UTR of buffalo PRNP gene provide binding sites for miRNAs post-transcriptional regulation.

ABSTRACT: Bovine spongiform encephalopathy, a member of transmissible spongiform encephalopathies, has not been reported in buffaloes, Bubalus bubalis. Prion protein (PrP), encoded by the prion protein gene (PRNP), is fundamental in the pathogenesis of transmissible spongiform encephalopathies. We previously showed that buffaloes express more PrP proteins but lower PRNP mRNA than cattle in several pivotal tissues like the obex. Therefore, we sought to establish whether genetic variability in PRNP 3'UTR, mediated by miRNA down-regulation, causes PrP expression differences between cattle and buffaloes. We annotated the 3'UTR of buffalo PRNP gene by 3'RACE experiment. A total of 92 fixed differences in the complete 3'UTR (~ 3 kb) were identified between 13 cattle and 13 buffaloes. Resequencing of UTR-C (g.786-1436) and UTR-B (g.778-1456) fragments confirmed that all mutations except g.1022T in cattle are fixed differences between 147 cattle and 146 buffaloes. In addition, analysis of the variation of ?G between cattle and buffalo sequences reveals four remarkable differences. Two buffalo-specific insertion sites (a 28-bp insertion and an AG insertion in buffalo 3'UTR of PRNP g.970-997 and g. 1088-1089, respectively) and two mutants (g. 1007-1008 TG?CC) create compatible binding sites for miRNAs in buffalo 3'UTR. This was validated through luciferase reporter assays which demonstrated that miR-125b-5p, miR-132-3p, miR-145-5p, miR-331-3p, and miR-338-3p directly act on the fixed difference sites in buffalo 3'UTR. Additional expressional analyses show that these five miRNAs are coexpressed with PRNP in bovine obex tissues. Our study reveals a miRNAs regulated mechanism explaining the differences in prion expression between cattle and buffalo.

SUBMITTER: Zhao H

PROVIDER: S-EPMC5542244 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Fixed differences in the 3'UTR of buffalo PRNP gene provide binding sites for miRNAs post-transcriptional regulation.

Zhao Hui H Wang Siqi S Guo Lixia L Du Yanli Y Liu Linlin L Ma Tengfei T Otecko Newton O NO Li Canpeng C Zhang Yaping Y

Oncotarget 20170701 28

Bovine spongiform encephalopathy, a member of transmissible spongiform encephalopathies, has not been reported in buffaloes, Bubalus bubalis. Prion protein (PrP), encoded by the prion protein gene (PRNP), is fundamental in the pathogenesis of transmissible spongiform encephalopathies. We previously showed that buffaloes express more PrP proteins but lower PRNP mRNA than cattle in several pivotal tissues like the obex. Therefore, we sought to establish whether genetic variability in PRNP 3'UTR, m ...[more]

PMID: 28545018

Similar Datasets

Project description:In contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate post-transcriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wild-type gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.

Dataset Information

Fixed differences in the 3'UTR of buffalo PRNP gene provide binding sites for miRNAs post-transcriptional regulation.

Publications

Fixed differences in the 3'UTR of buffalo PRNP gene provide binding sites for miRNAs post-transcriptional regulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets