DOI: 10.1073/pnas.1422273112. Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5

Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5

10.1073/pnas.1422273112

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Significance Inherited multisystemic diseases, myotonic dystrophies type 1 (DM1) and type 2 (DM2), are caused by long CUG and CCUG RNA repeats. The mutant RNA CCUG repeats should be degraded after intron excision; however, this RNA accumulates in cells, leading to pathology. Although mutant RNAs may be degraded with synthetic oligonucleotides, the identification of a cause of the increased stability of CUG and CCUG RNAs would help to improve the efficiency of their degradation. We found that the reduction of RNA helicase p68 in skeletal muscle biopsies of DM1 and DM2 patients contributes to the delay of degradation of the mutant RNAs. Our work suggests RNA helicase p68 as a therapeutic target in DM, correction of which improves degradation of the mutant RNAs, reducing DM pathology.

Bibliography

Jones, K., Wei, C., Schoser, B., Meola, G., Timchenko, N., & Timchenko, L. (2015). Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5. Proceedings of the National Academy of Sciences, 112(26), 8041â8045.

Authors 6

Karlie Jones (first)
Christina Wei (additional)
Benedikt Schoser (additional)
Giovanni Meola (additional)
Nikolai Timchenko (additional)
Lubov Timchenko (additional)

References 21 Referenced 30

PS Harper Myotonic Dystrophy (WB Saunders, London, 2001). / Myotonic Dystrophy by Harper PS (2001)
10.1016/0092-8674(92)90154-5
10.1126/science.1062125
10.1086/302268
10.1016/j.biocel.2013.06.010
10.1093/hmg/ddl181
10.1093/nar/24.22.4407
10.1093/hmg/5.1.115
10.1093/emboj/19.17.4439
10.1172/JCI64081
10.1073/pnas.0505873102
10.1074/jbc.M406415200
10.1083/jcb.201108113
10.1093/nar/gkr1228
O Pettersson, , DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1. Hum Mol Genet 42, 7186–7200 (2014). / Hum Mol Genet / DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1 by Pettersson O (2014)
10.1016/j.ajpath.2011.07.013
10.1074/jbc.M111.255224
10.1126/science.289.5485.1769
10.1074/jbc.M200182200
10.1038/nm.2374
G Meola, K Jones, C Wei, LT Timchenko, Dysfunction of protein homeostasis in myotonic dystrophies. Histol Histopathol 28, 1089–1098 (2013). / Histol Histopathol / Dysfunction of protein homeostasis in myotonic dystrophies by Meola G (2013)

Dates

Type	When
Created	10 years, 2 months ago (June 15, 2015, 11:01 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 12:20 a.m.)
Indexed	1 month, 1 week ago (July 20, 2025, midnight)
Issued	10 years, 2 months ago (June 15, 2015)
Published	10 years, 2 months ago (June 15, 2015)
Published Online	10 years, 2 months ago (June 15, 2015)
Published Print	10 years, 2 months ago (June 30, 2015)

Funders 3

NIH
Awards1
1. AR044387; AR052791; AR064488
NIH
Awards1
1. CA15942; DK102597; GM551888
FMM-Fondazione
Awards1
1. No number

BibTeX

@article{Jones_2015, title={Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5}, volume={112}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1422273112}, DOI={10.1073/pnas.1422273112}, number={26}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Jones, Karlie and Wei, Christina and Schoser, Benedikt and Meola, Giovanni and Timchenko, Nikolai and Timchenko, Lubov}, year={2015}, month=jun, pages={8041–8045} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        20
      ]
    ],
    "date-time": "2025-07-20T04:00:51Z",
    "timestamp": 1752984051362
  },
  "reference-count": 21,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "26",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2015,
            6,
            15
          ]
        ],
        "date-time": "2015-06-15T00:00:00Z",
        "timestamp": 1434326400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://www.pnas.org/site/misc/userlicense.xhtml"
    }
  ],
  "funder": [
    {
      "name": "NIH",
      "award": [
        "AR044387; AR052791; AR064488"
      ]
    },
    {
      "name": "NIH",
      "award": [
        "CA15942; DK102597; GM551888"
      ]
    },
    {
      "name": "FMM-Fondazione",
      "award": [
        "No number"
      ]
    }
  ],
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2015,
        6,
        30
      ]
    ]
  },
  "abstract": "<jats:title>Significance</jats:title>\n          <jats:p>Inherited multisystemic diseases, myotonic dystrophies type 1 (DM1) and type 2 (DM2), are caused by long CUG and CCUG RNA repeats. The mutant RNA CCUG repeats should be degraded after intron excision; however, this RNA accumulates in cells, leading to pathology. Although mutant RNAs may be degraded with synthetic oligonucleotides, the identification of a cause of the increased stability of CUG and CCUG RNAs would help to improve the efficiency of their degradation. We found that the reduction of RNA helicase p68 in skeletal muscle biopsies of DM1 and DM2 patients contributes to the delay of degradation of the mutant RNAs. Our work suggests RNA helicase p68 as a therapeutic target in DM, correction of which improves degradation of the mutant RNAs, reducing DM pathology.</jats:p>",
  "DOI": "10.1073/pnas.1422273112",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2015,
        6,
        16
      ]
    ],
    "date-time": "2015-06-16T03:01:21Z",
    "timestamp": 1434423681000
  },
  "page": "8041-8045",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 30,
  "title": "Reduction of toxic RNAs in myotonic dystrophies type 1 and type 2 by the RNA helicase p68/DDX5",
  "prefix": "10.1073",
  "volume": "112",
  "author": [
    {
      "given": "Karlie",
      "family": "Jones",
      "sequence": "first",
      "affiliation": [
        {
          "name": "National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;"
        }
      ]
    },
    {
      "given": "Christina",
      "family": "Wei",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Neurology, Cincinnati Children\u2019s Hospital and University of Cincinnati Medical Center, Cincinnati, OH 45219;"
        }
      ]
    },
    {
      "given": "Benedikt",
      "family": "Schoser",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-Universit\u00e4t, 80336 Munich, Germany;"
        }
      ]
    },
    {
      "given": "Giovanni",
      "family": "Meola",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Neurology, University of Milan, IRCCS Policlinico San Donato, 20097 Milan, Italy;"
        }
      ]
    },
    {
      "given": "Nikolai",
      "family": "Timchenko",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Surgery, Cincinnati Children\u2019s Hospital and University of Cincinnati Medical Center, Cincinnati, OH 45219"
        }
      ]
    },
    {
      "given": "Lubov",
      "family": "Timchenko",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Division of Neurology, Cincinnati Children\u2019s Hospital and University of Cincinnati Medical Center, Cincinnati, OH 45219;"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2015,
        6,
        15
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "volume-title": "Myotonic Dystrophy",
      "author": "Harper PS",
      "year": "2001",
      "unstructured": "PS Harper Myotonic Dystrophy (WB Saunders, London, 2001)."
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90154-5"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1062125"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1086/302268"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.biocel.2013.06.010"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/ddl181"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/24.22.4407"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/5.1.115"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/emboj/19.17.4439"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1172/JCI64081"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0505873102"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M406415200"
    },
    {
      "key": "e_1_3_3_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1083/jcb.201108113"
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gkr1228"
    },
    {
      "key": "e_1_3_3_15_2",
      "first-page": "7186",
      "article-title": "DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1",
      "volume": "42",
      "author": "Pettersson O",
      "year": "2014",
      "unstructured": "O Pettersson, , DDX6 regulates sequestered nuclear CUG-expanded DMPK-mRNA in dystrophia myotonica type 1. Hum Mol Genet 42, 7186\u20137200 (2014).",
      "journal-title": "Hum Mol Genet"
    },
    {
      "key": "e_1_3_3_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.ajpath.2011.07.013"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M111.255224"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.289.5485.1769"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M200182200"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm.2374"
    },
    {
      "key": "e_1_3_3_21_2",
      "first-page": "1089",
      "article-title": "Dysfunction of protein homeostasis in myotonic dystrophies",
      "volume": "28",
      "author": "Meola G",
      "year": "2013",
      "unstructured": "G Meola, K Jones, C Wei, LT Timchenko, Dysfunction of protein homeostasis in myotonic dystrophies. Histol Histopathol 28, 1089\u20131098 (2013).",
      "journal-title": "Histol Histopathol"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "http://www.pnas.org/syndication/doi/10.1073/pnas.1422273112",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.1422273112",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T04:20:46Z",
    "timestamp": 1649823646000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.1422273112"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2015,
        6,
        15
      ]
    ]
  },
  "references-count": 21,
  "journal-issue": {
    "issue": "26",
    "published-print": {
      "date-parts": [
        [
          2015,
          6,
          30
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.1422273112"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.1422273112",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2015,
        6,
        15
      ]
    ]
  },
  "assertion": [
    {
      "value": "2015-06-15",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}