English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan

Esslinger, S. M., Schwalb, B., Helfer, S., Michalik, K. M., Witte, H., Maier, K. C., et al. (2013). Drosophila miR-277 controls branched-chain amino acid catabolism and affects lifespan. RNA Biology, 10(6), 1042-1056. doi:10.4161/rna.24810.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-3C60-7 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-C50C-6
Genre: Journal Article

Files

show Files
hide Files
:
1922705.pdf (Publisher version), 3MB
Name:
1922705.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1922705-Suppl.pdf (Supplementary material), 6MB
Name:
1922705-Suppl.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Esslinger, S. M., Author
Schwalb, B., Author
Helfer, S., Author
Michalik, K. M., Author
Witte, H., Author
Maier, K. C., Author
Martin, D., Author
Michalke, B., Author
Tresch, A., Author
Cramer, P.1, Author              
Förstemann, K., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

Content

show
hide
Free keywords: miRNA, miRNA target validation, longevity, ageing, maple syrup urine disease (MSUD), metabolic syndrome, diabetes
 Abstract: Development, growth and adult survival are coordinated with available metabolic resources, ascertaining that the organism responds appropriately to environmental conditions. MicroRNAs are short (21–23 nt) regulatory RNAs that confer specificity on the RNA-induced silencing complex (RISC) to inhibit a given set of mRNA targets. We profiled changes in miRNA expression during adult life in Drosophila melanogaster and determined that miR-277 is downregulated during adult life. Molecular analysis revealed that this miRNA controls branched-chain amino acid (BCAA) catabolism and as a result it can modulate the activity of the TOR kinase, a central growth regulator, in cultured cells. Metabolite analysis in cultured cells as well as flies suggests that the mechanistic basis may be an accumulation of branched-chain α-keto-acids (BCKA), rather than BCAAs, thus avoiding potentially detrimental consequences of increased branched chain amino acid levels on e.g., translational fidelity. Constitutive miR-277 expression shortens lifespan and is synthetically lethal with reduced insulin signaling, indicating that metabolic control underlies this phenotype. Transgenic inhibition with a miRNA sponge construct also shortens lifespan, in particular on protein-rich food. Thus, optimal metabolic adaptation appears to require tuning of cellular BCAA catabolism by miR-277.

Details

show
hide
Language(s): eng - English
 Dates: 2013-04-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.4161/rna.24810
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: RNA Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 10 (6) Sequence Number: - Start / End Page: 1042 - 1056 Identifier: -