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Related Concept Videos

Regulated mRNA Transport02:22

Regulated mRNA Transport

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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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pre-mRNA Processing

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In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a “cap” to the 5’ end of the growing transcript. In this process, a 5’ phosphate is replaced by modified guanosine that has a methyl group attached to it (7-Methyl...
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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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mRNA Stability and Gene Expression02:51

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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TGF-beta1 mRNA upregulation influences chronic renal allograft dysfunction.

P Pribylova-Hribova1, K Kotsch, A Lodererova

  • 1Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. petra.hribova@medicon.cz

Kidney International
|April 14, 2006
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Transforming growth factor-beta1 (TGF-beta1) is elevated in kidney transplant rejection and dysfunction. This key molecule may play a significant role in chronic allograft nephropathy development.

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Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • Acute rejection (AR) is a major risk factor for chronic allograft nephropathy (CAN) after kidney transplantation.
  • CAN involves progressive interstitial fibrosis and is linked to increased transforming growth factor-beta1 (TGF-beta1) expression, but its kinetics remain unclear.

Purpose of the Study:

  • To investigate the role of intragraft TGF-beta1 expression in early graft dysfunction and its influence on late renal allograft dysfunction.

Main Methods:

  • Quantified TGF-beta1 mRNA expression in 174 human renal biopsies using real-time reverse transcriptase-polymerase chain reaction.
  • Correlated expression levels with Banff histopathological grades, TGF-beta1 immunohistology, and clinical outcomes.

Main Results:

  • TGF-beta1 was significantly upregulated in AR, CAN, and acute tubular necrosis with delayed graft function compared to controls.
  • Heightened TGF-beta1 expression was observed in borderline changes, recurrent glomerulonephritis, and cyclosporine toxicity.
  • TGF-beta1 overexpression in CAN correlated with an increased risk of renal allograft dysfunction at 18 months.

Conclusions:

  • Intragraft TGF-beta1 mRNA expression is significantly upregulated in both AR and CAN.
  • These findings support a key role for TGF-beta1 in the pathogenesis of chronic allograft dysfunction.