A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

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Standard

A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder. / Frankel, Lisa B; Di Malta, Chiara; Wen, Jiayu; Eskelinen, Eeva-Liisa; Ballabio, Andrea; Lund, Anders H.

I: Nature Communications, Bind 5, 5840, 2014.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Frankel, LB, Di Malta, C, Wen, J, Eskelinen, E-L, Ballabio, A & Lund, AH 2014, 'A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder', Nature Communications, bind 5, 5840. https://doi.org/10.1038/ncomms6840

APA

Frankel, L. B., Di Malta, C., Wen, J., Eskelinen, E-L., Ballabio, A., & Lund, A. H. (2014). A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder. Nature Communications, 5, [5840]. https://doi.org/10.1038/ncomms6840

Vancouver

Frankel LB, Di Malta C, Wen J, Eskelinen E-L, Ballabio A, Lund AH. A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder. Nature Communications. 2014;5. 5840. https://doi.org/10.1038/ncomms6840

Author

Frankel, Lisa B ; Di Malta, Chiara ; Wen, Jiayu ; Eskelinen, Eeva-Liisa ; Ballabio, Andrea ; Lund, Anders H. / A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder. I: Nature Communications. 2014 ; Bind 5.

Bibtex

@article{fadc7f53f5c34850b5a0bb205a100161,
title = "A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder",
abstract = "Sulfatases are key enzymatic regulators of sulfate homeostasis with several biological functions including degradation of glycosaminoglycans (GAGs) and other macromolecules in lysosomes. In a severe lysosomal storage disorder, multiple sulfatase deficiency (MSD), global sulfatase activity is deficient due to mutations in the sulfatase-modifying factor 1 (SUMF1) gene, encoding the essential activator of all sulfatases. We identify a novel regulatory layer of sulfate metabolism mediated by a microRNA. miR-95 depletes SUMF1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. This blocks autophagy-mediated degradation, causing cytoplasmic accumulation of autophagosomes and autophagic substrates. By targeting miR-95 in cells from MSD patients, we can effectively increase residual SUMF1 expression, allowing for reactivation of sulfatase activity and increased clearance of sulfated GAGs. The identification of this regulatory mechanism opens the opportunity for a unique therapeutic approach in MSD patients where the need for exogenous enzyme replacement is circumvented.",
author = "Frankel, {Lisa B} and {Di Malta}, Chiara and Jiayu Wen and Eeva-Liisa Eskelinen and Andrea Ballabio and Lund, {Anders H.}",
year = "2014",
doi = "10.1038/ncomms6840",
language = "English",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder

AU - Frankel, Lisa B

AU - Di Malta, Chiara

AU - Wen, Jiayu

AU - Eskelinen, Eeva-Liisa

AU - Ballabio, Andrea

AU - Lund, Anders H.

PY - 2014

Y1 - 2014

N2 - Sulfatases are key enzymatic regulators of sulfate homeostasis with several biological functions including degradation of glycosaminoglycans (GAGs) and other macromolecules in lysosomes. In a severe lysosomal storage disorder, multiple sulfatase deficiency (MSD), global sulfatase activity is deficient due to mutations in the sulfatase-modifying factor 1 (SUMF1) gene, encoding the essential activator of all sulfatases. We identify a novel regulatory layer of sulfate metabolism mediated by a microRNA. miR-95 depletes SUMF1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. This blocks autophagy-mediated degradation, causing cytoplasmic accumulation of autophagosomes and autophagic substrates. By targeting miR-95 in cells from MSD patients, we can effectively increase residual SUMF1 expression, allowing for reactivation of sulfatase activity and increased clearance of sulfated GAGs. The identification of this regulatory mechanism opens the opportunity for a unique therapeutic approach in MSD patients where the need for exogenous enzyme replacement is circumvented.

AB - Sulfatases are key enzymatic regulators of sulfate homeostasis with several biological functions including degradation of glycosaminoglycans (GAGs) and other macromolecules in lysosomes. In a severe lysosomal storage disorder, multiple sulfatase deficiency (MSD), global sulfatase activity is deficient due to mutations in the sulfatase-modifying factor 1 (SUMF1) gene, encoding the essential activator of all sulfatases. We identify a novel regulatory layer of sulfate metabolism mediated by a microRNA. miR-95 depletes SUMF1 protein levels and suppresses sulfatase activity, causing the disruption of proteoglycan catabolism and lysosomal function. This blocks autophagy-mediated degradation, causing cytoplasmic accumulation of autophagosomes and autophagic substrates. By targeting miR-95 in cells from MSD patients, we can effectively increase residual SUMF1 expression, allowing for reactivation of sulfatase activity and increased clearance of sulfated GAGs. The identification of this regulatory mechanism opens the opportunity for a unique therapeutic approach in MSD patients where the need for exogenous enzyme replacement is circumvented.

U2 - 10.1038/ncomms6840

DO - 10.1038/ncomms6840

M3 - Journal article

C2 - 25524633

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 5840

ER -

ID: 129101975