OpenLB
Open Library of Bioscience
Advanced Search
Biomedicines
Feb 27, 2023;11 (3):

Nonsense-Mediated mRNA Decay Factor Functions in Human Health and Disease.

Lingling Sun, Justine Mailliot, Christiane Schaffitzel
Author Information
  1. Lingling Sun: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK.
  2. Justine Mailliot: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK. ORCID
  3. Christiane Schaffitzel: School of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UK. ORCID
PMID: 36979701 DOI: 10.3390/biomedicines11030722

Abstract

Nonsense-mediated mRNA decay (NMD) is a cellular surveillance mechanism that degrades mRNAs with a premature stop codon, avoiding the synthesis of C-terminally truncated proteins. In addition to faulty mRNAs, NMD recognises ~10% of endogenous transcripts in human cells and downregulates their expression. The up-frameshift proteins are core NMD factors and are conserved from yeast to human in structure and function. In mammals, NMD diversified into different pathways that target different mRNAs employing additional NMD factors. Here, we review our current understanding of molecular mechanisms and cellular roles of NMD pathways and the involvement of more specialised NMD factors. We describe the consequences of mutations in NMD factors leading to neurodevelopmental diseases, and the role of NMD in cancer. We highlight strategies of RNA viruses to evade recognition and decay by the NMD machinery.

Keywords

cancer exon-junction complex neurodevelopmental disease nonsense-mediated mRNA decay up-frameshift proteins viral NMD evasion

References

  1. Mol Cell. 2011 May 20;42(4):500-10 [PMID: 21596314]
  2. Mol Cell. 2013 Jul 25;51(2):249-64 [PMID: 23810859]
  3. Cold Spring Harb Perspect Biol. 2019 Feb 1;11(2): [PMID: 29891560]
  4. Mol Cell. 2003 Apr;11(4):939-49 [PMID: 12718880]
  5. Biomolecules. 2020 Jul 04;10(7): [PMID: 32635561]
  6. EMBO J. 2003 Feb 3;22(3):641-50 [PMID: 12554664]
  7. Mol Brain. 2015 May 27;8:33 [PMID: 26012578]
  8. Hum Mol Genet. 2013 May 1;22(9):1816-25 [PMID: 23376982]
  9. PLoS One. 2017 Mar 21;12(3):e0173980 [PMID: 28323884]
  10. Mol Cell. 2004 Nov 19;16(4):597-607 [PMID: 15546619]
  11. Cell Host Microbe. 2014 Sep 10;16(3):403-11 [PMID: 25211080]
  12. EMBO J. 2019 Feb 1;38(3): [PMID: 30530525]
  13. RNA. 2006 Jun;12(6):1015-22 [PMID: 16601204]
  14. PLoS Biol. 2009 May 26;7(5):e1000120 [PMID: 19478851]
  15. EMBO Rep. 2004 Mar;5(3):304-10 [PMID: 14968132]
  16. RNA. 2011 Dec;17(12):2108-18 [PMID: 22028362]
  17. Adv Exp Med Biol. 2019;1157:41-83 [PMID: 31342437]
  18. Nat Genet. 2016 Oct;48(10):1112-8 [PMID: 27618451]
  19. Nat Commun. 2016 Aug 11;7:12434 [PMID: 27511142]
  20. Cell. 2009 May 1;137(3):536-48 [PMID: 19410547]
  21. Genes Dev. 2014 Nov 15;28(22):2498-517 [PMID: 25403180]
  22. Genes Dev. 2020 Aug 1;34(15-16):1075-1088 [PMID: 32616520]
  23. J Virol. 1993 Nov;67(11):6365-78 [PMID: 8411338]
  24. Nat Microbiol. 2019 Jun;4(6):985-995 [PMID: 30833725]
  25. Nucleic Acids Res. 2018 Mar 16;46(5):2648-2659 [PMID: 29378013]
  26. EMBO J. 2022 May 16;41(10):e108898 [PMID: 35403729]
  27. Curr Biol. 2006 Feb 21;16(4):433-9 [PMID: 16488880]
  28. Nature. 2010 May 13;465(7295):227-30 [PMID: 20463739]
  29. Cell. 2007 Oct 19;131(2):286-99 [PMID: 17956730]
  30. Cell. 2010 Dec 10;143(6):938-50 [PMID: 21145460]
  31. Nat Rev Mol Cell Biol. 2019 Jun;20(6):368-383 [PMID: 30940912]
  32. Nat Genet. 2019 Nov;51(11):1645-1651 [PMID: 31659324]
  33. Development. 2015 Jan 15;142(2):352-62 [PMID: 25503407]
  34. EMBO Rep. 2007 Jun;8(6):596-602 [PMID: 17468741]
  35. EMBO Rep. 2015 May;16(5):599-609 [PMID: 25807986]
  36. RNA. 2019 Apr;25(4):407-422 [PMID: 30655309]
  37. PLoS Pathog. 2021 May 21;17(5):e1009603 [PMID: 34019569]
  38. Front Oncol. 2020 Oct 28;10:580513 [PMID: 33251144]
  39. Genes Dev. 2014 Nov 15;28(22):2447-9 [PMID: 25403177]
  40. Nucleic Acids Res. 2012 Feb;40(3):1251-66 [PMID: 21965535]
  41. PLoS Pathog. 2023 Jan 5;19(1):e1011070 [PMID: 36603024]
  42. RNA. 2008 May;14(5):914-27 [PMID: 18369187]
  43. Nat Commun. 2020 Jul 3;11(1):3345 [PMID: 32620802]
  44. J Cell Sci. 2023 May 15;136(10): [PMID: 37218462]
  45. Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):624-33 [PMID: 23500037]
  46. Nat Genet. 2007 Sep;39(9):1127-33 [PMID: 17704778]
  47. Mol Cell Biol. 2011 Sep;31(17):3670-80 [PMID: 21730287]
  48. FEBS Lett. 2007 Jul 24;581(18):3485-8 [PMID: 17617410]
  49. Mol Cell. 2008 Feb 1;29(2):255-62 [PMID: 18243119]
  50. Genes Dev. 2009 May 1;23(9):1091-105 [PMID: 19417104]
  51. Eur J Med Genet. 2012 Aug-Sep;55(8-9):476-9 [PMID: 22609145]
  52. Mol Psychiatry. 2018 Aug;23(8):1773-1786 [PMID: 28948974]
  53. Nat Struct Mol Biol. 2009 Jan;16(1):49-55 [PMID: 19060897]
  54. Nat Commun. 2016 Jun 22;7:12070 [PMID: 27329342]
  55. Genet Med. 2019 Jul;21(7):1611-1620 [PMID: 30504930]
  56. Front Genet. 2020 Oct 16;11:580149 [PMID: 33193701]
  57. Science. 2001 Sep 7;293(5536):1836-9 [PMID: 11546874]
  58. Biochem Soc Trans. 2018 Jun 19;46(3):503-512 [PMID: 29626148]
  59. Nucleic Acids Res. 2016 Sep 19;44(16):7766-76 [PMID: 27418677]
  60. Microbes Infect. 2013 Jun;15(6-7):491-505 [PMID: 23541980]
  61. Cell. 2016 Apr 7;165(2):382-95 [PMID: 27040500]
  62. EMBO J. 2007 Jan 10;26(1):253-64 [PMID: 17159905]
  63. Nucleic Acids Res. 2014 Aug;42(14):9217-35 [PMID: 25053839]
  64. Am J Hum Genet. 2020 Dec 3;107(6):1178-1185 [PMID: 33242396]
  65. Clin Genet. 2013 Jun;83(6):560-4 [PMID: 22957832]
  66. Front Immunol. 2022 Sep 16;13:959962 [PMID: 36189216]
  67. Bioessays. 2012 Dec;34(12):1025-34 [PMID: 23108796]
  68. J Cell Biol. 2007 Sep 24;178(7):1145-60 [PMID: 17893241]
  69. Nucleic Acids Res. 2020 Jul 27;48(13):7468-7482 [PMID: 32542372]
  70. Nucleic Acids Res. 2018 Feb 16;46(3):1038-1051 [PMID: 29272451]
  71. Biomaterials. 2015 Oct;67:274-85 [PMID: 26231918]
  72. Semin Cell Dev Biol. 2018 Mar;75:78-87 [PMID: 28866327]
  73. J Virol. 2007 Dec;81(24):13578-86 [PMID: 17928342]
  74. Genes Dev. 2014 Sep 1;28(17):1900-16 [PMID: 25184677]
  75. J Virol. 2012 Jul;86(14):7530-43 [PMID: 22553336]
  76. Cell. 2013 Jun 6;153(6):1252-65 [PMID: 23746841]
  77. Nat Struct Mol Biol. 2008 Jan;15(1):85-93 [PMID: 18066079]
  78. Nucleic Acids Res. 2016 Feb 29;44(4):1909-23 [PMID: 26740584]
  79. Worm. 2013 Apr 1;2(2):e23005 [PMID: 24058870]
  80. Cancer Res. 2014 Jun 1;74(11):3104-13 [PMID: 24662918]
  81. Cell. 1995 Aug 11;82(3):475-83 [PMID: 7543368]
  82. EMBO J. 2022 May 16;41(10):e109202 [PMID: 35451102]
  83. RNA. 2000 Sep;6(9):1226-35 [PMID: 10999600]
  84. Front Oncol. 2020 Nov 06;10:595187 [PMID: 33240819]
  85. RNA. 2006 Oct;12(10):1817-24 [PMID: 16931876]
  86. Emerg Microbes Infect. 2019;8(1):1003-1016 [PMID: 31282298]
  87. Mol Cell Proteomics. 2016 May;15(5):1584-97 [PMID: 26896796]
  88. Nucleic Acids Res. 2021 Nov 8;49(19):11022-11037 [PMID: 34634811]
  89. Mol Psychiatry. 2010 Jul;15(7):767-76 [PMID: 19238151]
  90. EMBO J. 2022 May 16;41(10):e109191 [PMID: 35451084]
  91. RNA. 2008 Sep;14(9):1950-8 [PMID: 18676617]
  92. Hum Mol Genet. 2001 Jan 15;10(2):99-105 [PMID: 11152657]
  93. Trends Genet. 2021 Jul;37(7):657-668 [PMID: 33277042]
  94. Elife. 2020 Jul 22;9: [PMID: 32697194]
  95. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10157-E10166 [PMID: 30297408]
  96. Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444 [PMID: 34791371]
  97. Nature. 2021 Aug;596(7873):583-589 [PMID: 34265844]
  98. Mol Cell. 2015 Jan 22;57(2):329-340 [PMID: 25616068]
  99. Cell Rep. 2018 Nov 27;25(9):2431-2446.e7 [PMID: 30466796]
  100. Psychiatr Genet. 2012 Jun;22(3):150-1 [PMID: 21862950]
  101. Neuron. 2019 Nov 20;104(4):665-679.e8 [PMID: 31585809]
  102. Hum Mol Genet. 2020 Aug 29;29(15):2568-2578 [PMID: 32667670]
  103. Nucleic Acids Res. 2022 Nov 11;50(20):11876-11894 [PMID: 36370101]
  104. J Virol. 2013 Aug;87(16):8853-61 [PMID: 23785196]
  105. Mol Cell. 2017 Jul 20;67(2):239-251.e6 [PMID: 28669802]
  106. Trends Genet. 2021 Feb;37(2):143-159 [PMID: 33008628]
  107. Viruses. 2022 May 23;14(5): [PMID: 35632854]
  108. Genes Dev. 2006 Feb 1;20(3):355-67 [PMID: 16452507]
  109. Mol Med Rep. 2016 Jul;14(1):655-60 [PMID: 27221324]
  110. Nat Rev Cancer. 2022 Aug;22(8):437-451 [PMID: 35624152]
  111. Semin Cell Dev Biol. 2021 Mar;111:101-107 [PMID: 32553580]
  112. Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10050-5 [PMID: 20479275]
  113. Mol Psychiatry. 2011 Mar;16(3):238-9 [PMID: 20479756]
  114. RNA. 2003 Jan;9(1):77-87 [PMID: 12554878]
  115. Nucleic Acids Res. 2014 Aug;42(14):9447-60 [PMID: 25013172]
  116. Biomolecules. 2015 Oct 20;5(4):2808-39 [PMID: 26492277]
  117. Mol Cell. 2008 Apr 25;30(2):179-89 [PMID: 18439897]
  118. EMBO J. 2000 Dec 15;19(24):6860-9 [PMID: 11118221]
  119. Nucleic Acids Res. 2020 Sep 4;48(15):8626-8644 [PMID: 32621609]
  120. Nucleic Acids Res. 2015 Sep 3;43(15):7600-11 [PMID: 26130714]
  121. World J Virol. 2013 May 12;2(2):32-48 [PMID: 24175228]
  122. Cell. 2000 Jun 23;101(7):741-51 [PMID: 10892745]
  123. J Mol Cell Biol. 2021 Aug 4;13(4):269-281 [PMID: 33783512]
  124. J Virol. 2009 Mar;83(5):2119-29 [PMID: 19091866]
  125. Curr Biol. 2014 Feb 3;24(3):R107-8 [PMID: 24502780]
  126. mBio. 2018 Nov 6;9(6): [PMID: 30401782]
  127. RNA. 2006 Jan;12(1):102-10 [PMID: 16301601]
  128. Nat Commun. 2018 Jan 30;9(1):431 [PMID: 29382845]
  129. J Biol Chem. 2020 Aug 14;295(33):11613-11625 [PMID: 32571872]
  130. RNA. 1998 Feb;4(2):205-14 [PMID: 9570320]
  131. Cancers (Basel). 2020 Mar 24;12(3): [PMID: 32213869]
  132. J Virol. 2013 Sep;87(17):9486-500 [PMID: 23637410]
  133. PLoS Biol. 2008 Apr 29;6(4):e92 [PMID: 18447580]
  134. Nucleic Acids Res. 2014 Feb;42(4):2673-86 [PMID: 24271394]
  135. Retrovirology. 2019 Feb 7;16(1):3 [PMID: 30732620]
  136. Oncogenesis. 2018 Sep 19;7(9):70 [PMID: 30228267]
  137. Nat Commun. 2021 Jun 22;12(1):3849 [PMID: 34158508]
  138. EMBO J. 2017 Oct 16;36(20):2968-2986 [PMID: 28899899]
  139. Front Oncol. 2021 Feb 12;10:613102 [PMID: 33643914]
  140. EMBO J. 2001 Sep 3;20(17):4987-97 [PMID: 11532962]
  141. Front Genet. 2019 Oct 31;10:1074 [PMID: 31737052]
  142. Nat Struct Mol Biol. 2012 Apr 22;19(5):498-505, S1-2 [PMID: 22522823]
  143. Nucleic Acids Res. 2012 Feb;40(3):1160-73 [PMID: 21989405]
  144. Mol Cell. 2011 Mar 18;41(6):693-703 [PMID: 21419344]
  145. Nat Commun. 2016 Dec 23;7:14021 [PMID: 28008922]
  146. Mol Cell. 2004 Jun 4;14(5):585-98 [PMID: 15175154]
  147. EMBO J. 2009 Aug 5;28(15):2293-306 [PMID: 19556969]
  148. Cell. 2000 Dec 22;103(7):1121-31 [PMID: 11163187]
  149. Biochem J. 2022 May 13;479(9):973-993 [PMID: 35551602]
  150. Retrovirology. 2010 Aug 05;7:65 [PMID: 20687936]
  151. Nat Commun. 2015 Jul 03;6:7581 [PMID: 26138914]
  152. Science. 2015 Sep 25;349(6255):1483-9 [PMID: 26404825]
  153. Noncoding RNA. 2021 Jul 27;7(3): [PMID: 34449682]
  154. Nature. 2004 Nov 4;432(7013):112-8 [PMID: 15525991]
  155. Nat Struct Mol Biol. 2009 Jul;16(7):747-53 [PMID: 19503078]
  156. Mol Psychiatry. 2012 Nov;17(11):1103-15 [PMID: 22182939]
  157. Nucleic Acids Res. 2005 Feb 08;33(3):825-37 [PMID: 15701754]
  158. RNA. 2020 Nov;26(11):1509-1518 [PMID: 32699064]
  159. Cell Rep. 2014 Oct 23;9(2):555-68 [PMID: 25310981]
  160. Science. 2006 Sep 29;313(5795):1968-72 [PMID: 16931718]
  161. Cell. 2006 Aug 25;126(4):713-25 [PMID: 16923391]
  162. RNA. 2023 Feb;29(2):178-187 [PMID: 36456182]
  163. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9): [PMID: 33627408]
  164. J Virol. 1990 Jun;64(6):2519-29 [PMID: 2335812]
  165. Nucleic Acids Res. 2014 Aug;42(14):9334-49 [PMID: 25016523]
  166. Mol Biol Cell. 2021 Dec 1;32(22):ar38 [PMID: 34586879]
  167. RNA. 1999 Oct;5(10):1299-307 [PMID: 10573121]
  168. Nat Struct Mol Biol. 2007 Dec;14(12):1173-9 [PMID: 18026120]
  169. Nucleic Acids Res. 2013 Sep;41(17):8319-31 [PMID: 23828042]
  170. Mol Cell. 2005 Oct 7;20(1):65-75 [PMID: 16209946]
  171. Am J Med Genet A. 2022 Feb;188(2):648-657 [PMID: 34761517]
  172. Curr Opin Struct Biol. 2020 Dec;65:110-118 [PMID: 32688260]
  173. Mol Cell. 2022 Aug 4;82(15):2779-2796.e10 [PMID: 35675814]
  174. Cell. 2008 Apr 18;133(2):314-27 [PMID: 18423202]
  175. Nat Rev Mol Cell Biol. 2015 Nov;16(11):665-77 [PMID: 26397022]
  176. Cell Rep. 2018 May 15;23(7):2186-2198 [PMID: 29768215]
  177. J Virol. 2014 Aug;88(15):8565-78 [PMID: 24850728]
  178. Int J Mol Sci. 2021 Nov 25;22(23): [PMID: 34884553]
  179. Retrovirology. 2018 Jun 28;15(1):42 [PMID: 29954456]
  180. Nat Rev Mol Cell Biol. 2019 Jul;20(7):406-420 [PMID: 30992545]
  181. Cancer Res. 2021 Sep 1;81(17):4499-4513 [PMID: 34215620]
  182. Nature. 1989 Dec 14;342(6251):816-9 [PMID: 2481237]
  183. Mol Cell Biol. 2003 Jul;23(14):4805-13 [PMID: 12832468]
  184. Hum Genet. 2013 Dec;132(12):1383-93 [PMID: 23925499]
  185. Elife. 2016 Jan 08;5: [PMID: 26744779]
  186. Nat Cell Biol. 2021 Jan;23(1):40-48 [PMID: 33420492]
  187. Nat Struct Mol Biol. 2004 Apr;11(4):330-7 [PMID: 15004547]
  188. Mol Cell. 2003 Nov;12(5):1187-200 [PMID: 14636577]
  189. Chimia (Aarau). 2019 May 29;73(5):374-379 [PMID: 31118119]
  190. J Biol Chem. 2011 Feb 25;286(8):6641-9 [PMID: 21106535]
  191. Nature. 2020 Jul;583(7816):459-468 [PMID: 32353859]
  192. Hum Mutat. 2015 Dec;36(12):1197-204 [PMID: 26350204]
  193. Mol Cell. 2003 Sep;12(3):675-87 [PMID: 14527413]
  194. Mol Cell. 2015 Aug 6;59(3):413-25 [PMID: 26253027]
  195. Elife. 2020 May 29;9: [PMID: 32469312]
  196. Cell Physiol Biochem. 2017;42(6):2194-2206 [PMID: 28942451]
  197. RNA. 2022 Dec;28(12):1621-1642 [PMID: 36192133]
  198. Nucleic Acids Res. 2022 Jun 10;50(10):5934-5947 [PMID: 35640974]

Grants

  1. /Wellcome Trust
  2. 210701/Z/18/Z/Wellcome Trust
Journal Article Review
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0NMDfactorsmRNAdecaymRNAsproteinscellularhumanup-frameshiftdifferentpathwaysneurodevelopmentalcancerNonsense-mediatedsurveillancemechanismdegradesprematurestopcodonavoidingsynthesisC-terminallytruncatedadditionfaultyrecognises~10%endogenoustranscriptscellsdownregulatesexpressioncoreconservedyeaststructurefunctionmammalsdiversifiedtargetemployingadditionalreviewcurrentunderstandingmolecularmechanismsrolesinvolvementspecialiseddescribeconsequencesmutationsleadingdiseasesrolehighlightstrategiesRNAvirusesevaderecognitionmachineryNonsense-MediatedDecayFactorFunctionsHumanHealthDiseaseexon-junctioncomplexdiseasenonsense-mediatedviralevasion

Similar Articles

Cited By