Poly(A) tail shortening correlates with mRNA repression in tropoelastin regulation

Hagmeister, U.; Reuschlein, Katja; März, A.; Wenck, Horst; Gallinat, Stefan; Lucius, Ralph; Knott, Anja

doi:10.1016/j.jdermsci.2012.03.001

Cited by 7 publications

(7 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to mice (26), we did not observe a marked increase in the miR-29 family of miRNAs in adult human aortae; this might reflect a species-specific difference or be a result of the number of samples or time points we tested. On the other hand, consistent with increased ELN mRNA degradation, both the proximal and distal poly(A) tails of ELN mRNA were shorter in adult aortae than that in fetal aortae; this agrees with findings in other elastin-rich human tissues (24) and affirms decreased ELN mRNA stability as a factor underlying the reduced postnatal levels of ELN mRNA in the aorta.…”

Section: Discussionsupporting

confidence: 88%

“…Similar to findings in other tissues (24), our quantification of ELN pre-mRNA in human fetal and adult aortae demonstrated only a 1.8-fold decrease in adult ELN transcription. Consistent with this steady transcription of ELN, we did not detect marked changes in the mRNA levels of known ELN transcriptional regulators or in methylation of the proximal ELN promoter.…”

Section: Discussionsupporting

confidence: 88%

“…Prior comparison of ELN mRNA in adult vs. fetal human skin, uterus, and lung showed that the transcripts from adult tissue have shorter poly(A) tails (24). To determine if this also occurred in the human aorta, we compared the mRNA poly(A) tail length of ELN aortic transcripts terminating at the proximal and distal polyadenylation sites and observed that both adult ELN transcripts had shorter poly(A) tails than the respective fetal transcripts (Figure 6).…”

Section: Eln Mrna Poly(a) Tail Length In the Aorta Shortens With Devementioning

confidence: 99%

“…The cDNA was then diluted 1:1 with water and 2 μl was used for each PCR. ELN mRNA has two poly(A) sites as previously described (24). To amplify the ELN mRNA poly(A) tails, the universal primer supplied by the manufacturer and forward primer I or forward primer II were used to amplify transcripts terminating at the proximal and distal or only distal polyadenylation site(s), respectively.…”

Section: Articles Morimoto Et Almentioning

confidence: 99%

“…Based on the study of fetal and postnatal rat lung (23) and fetal and postnatal human skin (24), ELN precursor messenger RNA (pre-mRNA) levels remain stable despite the postnatal decline in steady-state levels of ELN messenger RNA (mRNA). Identified posttranscriptional mechanisms of ELN gene regulation include regulation by microRNAs (miRNAs) (25)(26)(27) and poly(A) tail degradation (24).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

Morimoto

Wang

et al. 2015

Pediatr Res

View full text Add to dashboard Cite

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD)is an autosomal recessive disorder caused by mutations in SMARCAL1. A frequent complication is arteriosclerosis associated with reduced elastin expression; however, the mechanism underlying the reduced elastin expression remains unknown. METHODS: Expression of transcriptional regulators of elastin (ELN) and microRNA (miRNA) regulators of ELN messenger RNA (mRNA), ELN promoter methylation, and ELN mRNA poly(A) tail length were assessed by quantitative RT-PCR, bisulfite Sanger sequencing, and the Poly(A) Tail Length Assay Kit, respectively, in unaffected developing human aortae and in an SIOD aorta. RESULTS: Comparing unaffected fetal and adult aortae, ELN precursor mRNA (pre-mRNA) levels remained nearly constant, whereas mRNA levels declined by ~10 2 -fold. This corresponded with a reduction in poly(A) tail length but not with changes in the other parameters. In contrast, compared to the unaffected fetal aortae, the SIOD aorta had 18-fold less ELN pre-mRNA and 10 4 -fold less mRNA. This corresponded with increased expression of miRNA regulators and shorter ELN mRNA poly(A) tail lengths but not with altered expression of ELN transcriptional regulators or ELN promoter methylation. CONCLUSION: Posttranscriptional mechanisms account for the reduction in ELN mRNA levels in unaffected aortae, whereas transcriptional and posttranscriptional mechanisms reduce elastin expression in SIOD aorta and predispose to arteriosclerosis.S chimke immuno-osseous dysplasia (SIOD, OMIM 242900) is a rare autosomal recessive multisystemic disorder caused by mutations in the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) gene (1). SMARCAL1 functions as a DNA-dependent annealing helicase (2) that recognizes single-stranded to double-stranded DNA transitions and binds to transcriptionally active chromatin (3). SMARCAL1 is involved in the DNA stress response (4,5), the reactivation of stalled replication forks (6)(7)(8), and the modulation of gene expression (3). Key manifestations of the disease include growth failure due to spondyloepiphyseal dysplasia, renal failure due to focal segmental glomerulosclerosis, T-cell immunodeficiency, facial dysmorphism, and hyperpigmented macules (9). Approximately 50% of SIOD patients also develop vascular disease (10), and the vascular complications are refractory to treatment and a common cause of death (11).The vascular disease in SIOD manifests as migraine-like headaches, transient ischemic attacks, and cerebrovascular accidents (11). The arterial histopathology shows intimal and medial hyperplasia, smooth muscle cell hyperplasia, and fragmented and disorganized elastin fibers (10,12). Molecular studies suggest reduced elastogenesis (10); however, the mechanism underlying this remains unknown.Elastin, which is critical for the development and maintenance of the arteries (13,14), confers the elastic recoil properties required for the proper function of the arteries as well as other load-bearing...

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 88%

Section: Eln Mrna Poly(a) Tail Length In the Aorta Shortens With Devementioning

confidence: 99%

Section: Articles Morimoto Et Almentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

Morimoto

Wang

et al. 2015

Pediatr Res

View full text Add to dashboard Cite

show abstract

A tissue‐engineered human dermal construct utilizing fibroblasts and transforming growth factor β1 to promote elastogenesis

Sommer¹,

Sattler²,

Weise³

et al. 2013

Biotechnology Journal

View full text Add to dashboard Cite

Numerous studies have shown that extracellular matrix (ECM)-based scaffolds are suitable for dermal constructs for the differentiation of various cell types in vitro and for constructive tissue remodeling after implantation in vivo. However, a shortcoming of these ECM materials is its limited elastogenesis. Elastic fibers constitute an essential component of mammalian connective tissue and the presence of elastic fibers is crucial for the proper function of the cardiovascular, pulmonary, and intestinal systems. Since it is still largely unknown how cells coordinate the molecular events of elastic-fiber assembly, understanding the ability to regenerate elastic fibers in tissues remains a significant challenge. For this reason, human neonatal dermal fibroblasts (HDFneo) were analyzed for their potential to serve as a cell culture model for elastic fiber assembly. Using optical technologies such as multiphoton laser-scanning microscopy (MPSLM) we demonstrate that HDFneo stimulated with transforming growth factor β1 (TGF-β1) are able to produce a distinct and complex elastic fiber system in vitro. As shown by the desmosine and isodesmosine content, crosslinked elastic fibers were formed within the 3D ECM-based scaffold. This tissue-engineered dermal construct may prove to be an effective template for the development of medicinal approaches in regenerative soft skin tissue reconstruction through TGF-β1 induction.

show abstract

Structural Proteins | The Biochemistry of Elastin

Keeley

2021

Encyclopedia of Biological Chemistry III

View full text Add to dashboard Cite

Poly(A) tail shortening correlates with mRNA repression in tropoelastin regulation

Cited by 7 publications

References 36 publications

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

Transcriptional and posttranscriptional mechanisms contribute to the dysregulation of elastogenesis in Schimke immuno-osseous dysplasia

A tissue‐engineered human dermal construct utilizing fibroblasts and transforming growth factor β1 to promote elastogenesis

Structural Proteins | The Biochemistry of Elastin

Contact Info

Product

Resources

About