MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway

Davide Cacchiarelli; Julie Martone; Erika Girardi; Marcella Cesana; Tania Incitti; Mariangela Morlando; Carmine Nicoletti; Tiziana Santini; Olga Sthandier; Laura Barberi; Alberto Auricchio; Antonio Musar; Irene Bozzoni

doi:10.1016/j.cmet.2010.07.008

MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway

Davide Cacchiarelli
, Julie Martone
, Erika Girardi
, Marcella Cesana
, Tania Incitti
, Mariangela Morlando
, Carmine Nicoletti
, Tiziana Santini
, Olga Sthandier
, Laura Barberi
, Alberto Auricchio
, Antonio Musar
, Irene Bozzoni

Research output: Contribution to journal › Article › peer-review

221 Scopus citations

Abstract

In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.

Original language	English (US)
Pages (from-to)	341-351
Number of pages	11
Journal	Cell Metabolism
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2010.07.008
State	Published - Oct 6 2010
Externally published	Yes

Bibliographical note

Funding Information:
We thank Prof. A. Riccio, Dr. M. Mora, Prof. P. Paggi, and Dr. L. Lombardi for providing material; Dr. De Angelis for helpful discussion; and Marcella Marchioni for technical support. D.C. is a recipient of a Microsoft research PhD fellowship. This work was partially supported by grants from Telethon (GGP07049 to I.B. and GGP06119 to A.M.); Parent Project Italia, EU project SIROCCO (LSHG-CT-2006-037900); ESF project “NuRNASu,” IIT “SEED,” PRIN, and BEMM; Fondazione Roma, EU project-Myoage, AFM (to A.M.); and AFM and EU projects Clinigene and DiMi (to A.A.).

Keywords

DEVBIO
DNA
HUMDISEASE

Publisher link

10.1016/j.cmet.2010.07.008

Find It

Find It at U of M Libraries

Cite this

Cacchiarelli, D., Martone, J., Girardi, E., Cesana, M., Incitti, T., Morlando, M., Nicoletti, C., Santini, T., Sthandier, O., Barberi, L., Auricchio, A., Musar, A., & Bozzoni, I. (2010). MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway. Cell Metabolism, 12(4), 341-351. https://doi.org/10.1016/j.cmet.2010.07.008

Cacchiarelli, D, Martone, J, Girardi, E, Cesana, M, Incitti, T, Morlando, M, Nicoletti, C, Santini, T, Sthandier, O, Barberi, L, Auricchio, A, Musar, A & Bozzoni, I 2010, 'MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway', Cell Metabolism, vol. 12, no. 4, pp. 341-351. https://doi.org/10.1016/j.cmet.2010.07.008

@article{6148390c1ffc4e68851217aaebd1abac,

title = "MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway",

abstract = "In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.",

keywords = "DEVBIO, DNA, HUMDISEASE",

author = "Davide Cacchiarelli and Julie Martone and Erika Girardi and Marcella Cesana and Tania Incitti and Mariangela Morlando and Carmine Nicoletti and Tiziana Santini and Olga Sthandier and Laura Barberi and Alberto Auricchio and Antonio Musar and Irene Bozzoni",

note = "Funding Information: We thank Prof. A. Riccio, Dr. M. Mora, Prof. P. Paggi, and Dr. L. Lombardi for providing material; Dr. De Angelis for helpful discussion; and Marcella Marchioni for technical support. D.C. is a recipient of a Microsoft research PhD fellowship. This work was partially supported by grants from Telethon (GGP07049 to I.B. and GGP06119 to A.M.); Parent Project Italia, EU project SIROCCO (LSHG-CT-2006-037900); ESF project “NuRNASu,” IIT “SEED,” PRIN, and BEMM; Fondazione Roma, EU project-Myoage, AFM (to A.M.); and AFM and EU projects Clinigene and DiMi (to A.A.). ",

year = "2010",

month = oct,

day = "6",

doi = "10.1016/j.cmet.2010.07.008",

language = "English (US)",

volume = "12",

pages = "341--351",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway

AU - Cacchiarelli, Davide

AU - Martone, Julie

AU - Girardi, Erika

AU - Cesana, Marcella

AU - Incitti, Tania

AU - Morlando, Mariangela

AU - Nicoletti, Carmine

AU - Santini, Tiziana

AU - Sthandier, Olga

AU - Barberi, Laura

AU - Auricchio, Alberto

AU - Musar, Antonio

AU - Bozzoni, Irene

N1 - Funding Information: We thank Prof. A. Riccio, Dr. M. Mora, Prof. P. Paggi, and Dr. L. Lombardi for providing material; Dr. De Angelis for helpful discussion; and Marcella Marchioni for technical support. D.C. is a recipient of a Microsoft research PhD fellowship. This work was partially supported by grants from Telethon (GGP07049 to I.B. and GGP06119 to A.M.); Parent Project Italia, EU project SIROCCO (LSHG-CT-2006-037900); ESF project “NuRNASu,” IIT “SEED,” PRIN, and BEMM; Fondazione Roma, EU project-Myoage, AFM (to A.M.); and AFM and EU projects Clinigene and DiMi (to A.A.).

PY - 2010/10/6

Y1 - 2010/10/6

N2 - In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.

AB - In Duchenne muscular dystrophy (DMD) the absence of dystrophin at the sarcolemma delocalizes and downregulates nitric oxide synthase (nNOS); this alters S-nitrosylation of HDAC2 and its chromatin association. We show that the differential HDAC2 nitrosylation state in Duchenne versus wild-type conditions deregulates the expression of a specific subset of microRNA genes. Several circuitries controlled by the identified microRNAs, such as the one linking miR-1 to the G6PD enzyme and the redox state of cell, or miR-29 to extracellular proteins and the fibrotic process, explain some of the DMD pathogenetic traits. We also show that, at variance with other myomiRs, miR-206 escapes from the dystrophin-nNOS control being produced in activated satellite cells before dystrophin expression; in these cells, it contributes to muscle regeneration through repression of the satellite specific factor, Pax7. We conclude that the pathway activated by dystrophin/nNOS controls several important circuitries increasing the robustness of the muscle differentiation program.

KW - DEVBIO

KW - DNA

KW - HUMDISEASE

UR - https://www.scopus.com/pages/publications/77957685944

UR - https://www.scopus.com/pages/publications/77957685944#tab=citedBy

U2 - 10.1016/j.cmet.2010.07.008

DO - 10.1016/j.cmet.2010.07.008

M3 - Article

C2 - 20727829

AN - SCOPUS:77957685944

SN - 1550-4131

VL - 12

SP - 341

EP - 351

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -

MicroRNAs involved in molecular circuitries relevant for the duchenne muscular dystrophy pathogenesis are controlled by the dystrophin/nNOS pathway

Abstract

Bibliographical note

Keywords

Publisher link

Find It

Other files and links

Fingerprint

Cite this