The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products

Zhu, Hanqing; Gao, Feng‐Hou

doi:10.7150/ijbs.21637

Cited by 20 publications

(25 citation statements)

References 54 publications

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“…In Xenopus , for instance, USP2–45 can deubiquitylate epithelial Na + channels in oocytes, while USP2–69 cannot perform such function due to differences in their N-terminal domains. In humans, functional differences have been also observed with regard to the implication of USP2 isoforms in cell cycle progression and antiviral response [ 43 ], but unfortunately no such data are currently available for pigs.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of mRNA isoforms in the skeletal muscle of pigs with distinct growth and fatness profiles

et al. 2018

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BackgroundThe identification of genes differentially expressed in the skeletal muscle of pigs displaying distinct growth and fatness profiles might contribute to identify the genetic factors that influence the phenotypic variation of such traits. So far, the majority of porcine transcriptomic studies have investigated differences in gene expression at a global scale rather than at the mRNA isoform level. In the current work, we have investigated the differential expression of mRNA isoforms in the gluteus medius (GM) muscle of 52 Duroc HIGH (increased backfat thickness, intramuscular fat and saturated and monounsaturated fatty acids contents) and LOW pigs (opposite phenotype, with an increased polyunsaturated fatty acids content).ResultsOur analysis revealed that 10.9% of genes expressed in the GM muscle generate alternative mRNA isoforms, with an average of 2.9 transcripts per gene. By using two different pipelines, one based on the CLC Genomics Workbench and another one on the STAR, RSEM and DESeq2 softwares, we have identified 10 mRNA isoforms that both pipelines categorize as differentially expressed in HIGH vs LOW pigs (P-value < 0.01 and ±0.6 log2fold-change). Only five mRNA isoforms, produced by the ITGA5, SEMA4D, LITAF, TIMP1 and ANXA2 genes, remain significant after correction for multiple testing (q-value < 0.05 and ±0.6 log2fold-change), being upregulated in HIGH pigs.ConclusionsThe increased levels of specific ITGA5, LITAF, TIMP1 and ANXA2 mRNA isoforms in HIGH pigs is consistent with reports indicating that the overexpression of these four genes is associated with obesity and metabolic disorders in humans. A broader knowledge about the functional attributes of these mRNA variants would be fundamental to elucidate the consequences of transcript diversity on the determinism of porcine phenotypes of economic interest.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4515-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Differential expression of mRNA isoforms in the skeletal muscle of pigs with distinct growth and fatness profiles

et al. 2018

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“…The UCH domain is a thiol protease that hydrolyzes the C‐terminal glycine peptide bond in ubiquitin 6,14 . Interestingly, the PHD2 and PHD3 domains of KMT2A, which are included in the extended N‐terminal portion of the chimeric fusion, are able to bind to E3‐ubiquitin ligases including CDC34 and ASB2, which have been shown to control the steady‐state stability of the KMT2A protein 18 . USP2 belongs to large family of deubiquitinating proteins and has been experimentally shown to deubiquinate and stabilize MDM2, leading to p53 degradation and activation of MYC 6,19 .…”

Section: Resultsmentioning

confidence: 99%

“…USP2 belongs to large family of deubiquitinating proteins and has been experimentally shown to deubiquinate and stabilize MDM2, leading to p53 degradation and activation of MYC 6,19 . Additionally, USP2 deubiquinates Cyclin A1, leading to cell cycle progression 18 . USP8 is an essential deubiquitinating enzyme with several functions including regulation of protein trafficking and stability and also endosomal sorting of transmembrane receptors and receptor tyrosine kinases through interaction with the ESCRT machinery 20 .…”

Section: Resultsmentioning

confidence: 99%

Cryptic and atypical KMT2A‐USP2 and KMT2A‐USP8 rearrangements identified by mate pair sequencing in infant and childhood leukemia

Blackburn

Smadbeck

Znoyko

et al. 2020

Genes Chromosomes & Cancer

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Infant leukemias are a rare group of neoplasms that are clinically and biologically distinct from their pediatric and adult counterparts. Unlike leukemia in older children where survival rates are generally favorable, infants with leukemia have a 5-year eventfree survival rate of <50%. The majority of infant leukemias are characterized by KMT2A (MLL) rearrangements (~70 to 80% in acute lymphoblastic leukemia), which appear to be drivers of early leukemogenesis. In this report, we describe three cases: a 9-month-old female infant with B-acute lymphoblastic leukemia (B-ALL), an 8-month-old female presenting with B/myeloid mixed phenotype acute leukemia (MPAL), and a 16-month-old male with B-ALL. The first case had a normal karyotype and B-ALL FISH results consistent with an atypical KMT2A rearrangement. The second case had trisomy 10 as the sole chromosomal abnormality and a normal KMT2A FISH result. Case 3 had trisomy 8 and a t (11;15)(q23;q21), an atypical KMT2A rearrangement by FISH studies, and a focal deletion of 15q with a breakpoint within the USP8 gene by chromosomal microarray. Mate pair sequencing was performed on all three cases and identified a KMT2A-USP2 rearrangement (cases 1 and 2) or a KMT2A-USP8 rearrangement (case 3). These recently characterized KMT2A fusions have been described exclusively in infant and pediatric leukemia cases where the incidence varies vary according to leukemia subtype, are considered high-risk, with a high incidence of central nervous system involvement, poor response to initial prednisone treatment, and poor event free survival. Additionally, approximately half of cases are unable to be resolved using standard cytogenetic approaches and are likely under recognized. Therefore, targeted molecular approaches are suggested in genetically unresolved infant leukemia cases to characterize these prognostically relevant clones. K E Y W O R D S B-lymphoblastic leukemia/lymphoma (B-ALL/LBL), infant leukemia, KMT2A, mixed-phenotype acute leukemia (MPAL), USP2, USP8

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“…This chimeric transcript can potentially contribute to leukemogenesis through several mechanisms: (a) dominant negative inhibition of wild‐type KMT2A transcription activation activity, (b) USP2 ‐mediated stabilization of KMT2A to protect from ubiquitin‐proteasome degradation, and (c) deubiquitination of Ub‐cyclin D1, thereby altering cell cycle progression from the G1 to the S phase …”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome sequencing reveals a KMT2A‐USP2 fusion in infant acute myeloid leukemia

Ikeda

Shiba

Tsujimoto

et al. 2019

Genes Chromosomes & Cancer

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The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products

Cited by 20 publications

References 54 publications

Differential expression of mRNA isoforms in the skeletal muscle of pigs with distinct growth and fatness profiles

Differential expression of mRNA isoforms in the skeletal muscle of pigs with distinct growth and fatness profiles

Cryptic and atypical KMT2A‐USP2 and KMT2A‐USP8 rearrangements identified by mate pair sequencing in infant and childhood leukemia

Whole transcriptome sequencing reveals a KMT2A‐USP2 fusion in infant acute myeloid leukemia

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