Редактирование: PABPN1

Polyadenylate-binding protein 2 (PABP-2) (Poly(A)-binding protein 2) (Nuclear poly(A)-binding protein 1) (Poly(A)-binding protein II) (PABII) (Polyadenylate-binding nuclear protein 1) [PAB2] [PABP2]

==Publications==

{{medline-entry
|title=Dysfunctional transcripts are formed by alternative polyadenylation in OPMD.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29088723
|abstract=Post-transcription mRNA processing in the 3'-untranslated region (UTR) of transcripts alters mRNA landscape. Alternative polyadenylation (APA) utilization in the 3'-UTR often leads to shorter 3'-UTR affecting mRNA stability, a process that is regulated by [[PABPN1]]. In skeletal muscles [[PABPN1]] levels reduce with age and a greater decrease in found in Oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant myopathy caused by expansion mutation in [[PABPN1]]. In OPMD models a shift from distal to proximal polyadenylation site utilization in the 3'-UTR, and [[PABPN1]] was shown to play a prominent role in APA. Whether [[PABPN1]]-mediated APA transcripts are functional is not fully understood. We investigate nuclear export and translation efficiency of transcripts in OPMD models. We focused on autophagy-regulated genes (ATGs) with APA utilization in cell models with reduced functional [[PABPN1]]. We provide evidence that ATGs transcripts from distal PAS retain in the nucleus and thus have reduced translation efficiency in cells with reduced [[PABPN1]]. In contrast, transcripts from proximal PAS showed a higher cytoplasmic abundance but a reduced occupancy in the ribosome. We therefore suggest that in reduced [[PABPN1]] levels ATG transcripts from APA may not effectively translate to proteins. In those conditions we found constitutive autophagosome fusion and reduced autophagy flux. Augmentation of [[PABPN1]] restored autophagosome fusion, suggesting that [[PABPN1]]-mediated APA plays a role in autophagy in OPMD and in aging muscles.

|keywords=* Gerotarget
* PABPN1
* aging muscles
* alternative polyadenylation site
* autophagy
* mRNA processing
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650278
}}
{{medline-entry
|title=[[PABPN1]]-Dependent mRNA Processing Induces Muscle Wasting.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27152426
|abstract=Poly(A) Binding Protein Nuclear 1 ([[PABPN1]]) is a multifunctional regulator of mRNA processing, and its expression levels specifically decline in aging muscles. An expansion mutation in [[PABPN1]] is the genetic cause of oculopharyngeal muscle dystrophy (OPMD), a late onset and rare myopathy. Moreover, reduced [[PABPN1]] expression correlates with symptom manifestation in OPMD. [[PABPN1]] regulates alternative polyadenylation site (PAS) utilization. However, the impact of PAS utilization on cell and tissue function is poorly understood. We hypothesized that altered [[PABPN1]] expression levels is an underlying cause of muscle wasting. To test this, we stably down-regulated [[PABPN1]] in mouse tibialis anterior (TA) muscles by localized injection of adeno-associated viruses expressing shRNA to [[PABPN1]] (shPab). We found that a mild reduction in [[PABPN1]] levels causes muscle pathology including myofiber atrophy, thickening of extracellular matrix and myofiber-type transition. Moreover, reduced [[PABPN1]] levels caused a consistent decline in distal PAS utilization in the 3'-UTR of a subset of OPMD-dysregulated genes. This alternative PAS utilization led to up-regulation of Atrogin-1, a key muscle atrophy regulator, but down regulation of proteasomal genes. Additionally reduced [[PABPN1]] levels caused a reduction in proteasomal activity, and transition in MyHC isotope expression pattern in myofibers. We suggest that [[PABPN1]]-mediated alternative PAS utilization plays a central role in aging-associated muscle wasting.
|mesh-terms=* Aging
* Animals
* Dependovirus
* Gene Expression Regulation
* Humans
* Mice
* Muscle Proteins
* Muscle, Skeletal
* Muscular Dystrophy, Oculopharyngeal
* Poly(A)-Binding Protein I
* RNA, Messenger
* SKP Cullin F-Box Protein Ligases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859507
}}
{{medline-entry
|title=A novel feed-forward loop between [[ARIH2]] E3-ligase and [[PABPN1]] regulates aging-associated muscle degeneration.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24486325
|abstract=Alanine expansion mutations in poly(A)-binding protein nuclear 1 ([[PABPN1]]) cause muscle weakness in the late-onset disorder oculopharyngeal muscular dystrophy. In affected muscles, expanded [[PABPN1]] forms nuclear aggregates, depleting levels of soluble [[PABPN1]] and inducing a genome-wide shift from distal to proximal polyadenylation site usage. [[PABPN1]] protein accumulation is regulated by the ubiquitin proteasome system, which is highly dysregulated in oculopharyngeal muscular dystrophy. We show that [[ARIH2]] E3-ligase regulates [[PABPN1]] protein accumulation and aggregation. Levels of [[ARIH2]] mRNA are regulated by [[PABPN1]] via proximal polyadenylation site usage. We demonstrate that masking the proximal polyadenylation site in [[ARIH2]] 3' untranslated region by antisense oligonucleotides elevates the expression of [[ARIH2]] and [[PABPN1]] and restores myogenic defects that are induced by [[ARIH2]] or [[PABPN1]] down-regulation in cell culture. In vivo [[ARIH2]] mRNA levels significantly decrease from midlife in vastus lateralis muscles and highly correlate with muscle degeneration. We suggest that the expression of both genes is maintained by a feed-forward loop between mRNA stability regulated by [[PABPN1]] and protein turnover regulated by [[ARIH2]]. 
|mesh-terms=* Aging
* Animals
* Blotting, Western
* Cell Line
* Gene Expression Regulation
* Humans
* Immunohistochemistry
* Immunoprecipitation
* Muscle, Skeletal
* Muscular Dystrophy, Oculopharyngeal
* Oligonucleotide Array Sequence Analysis
* Poly(A)-Binding Protein I
* Reverse Transcriptase Polymerase Chain Reaction
* Transfection
* Ubiquitin-Protein Ligases

|full-text-url=https://sci-hub.do/10.1016/j.ajpath.2013.12.011
}}
{{medline-entry
|title=A decline in [[PABPN1]] induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23793615
|abstract=Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 ([[PABPN1]]). [[PABPN1]] is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-[[PABPN1]] at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-[[PABPN1]], instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in [[PABPN1]] levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in [[PABPN1]] accelerated in OPMD and was specific to skeletal muscles. Reduced [[PABPN1]] levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to [[PABPN1]] expression levels. We suggest that [[PABPN1]] levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder. 
|mesh-terms=* Adolescent
* Adult
* Aged, 80 and over
* Aging
* Animals
* Case-Control Studies
* Cellular Senescence
* Gene Expression Regulation
* Humans
* Mice
* Middle Aged
* Muscle Weakness
* Muscle, Skeletal
* Muscular Dystrophy, Oculopharyngeal
* Poly(A)-Binding Protein I
* RNA, Messenger
* Transcriptome
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824410
}}