The RNA Revolution in the Central Molecular Biology Dogma Evolution.

William A Haseltine, Roberto Patarca
Author Information
  1. William A Haseltine: Access Health International, 384 West Lane, Ridgefield, CT 06877, USA.
  2. Roberto Patarca: Access Health International, 384 West Lane, Ridgefield, CT 06877, USA. ORCID

Abstract

Human genome projects in the 1990s identified about 20,000 protein-coding sequences. We are now in the RNA revolution, propelled by the realization that genes determine phenotype beyond the foundational central molecular biology dogma, stating that inherited linear pieces of DNA are transcribed to RNAs and translated into proteins. Crucially, over 95% of the genome, initially considered junk DNA between protein-coding genes, encodes essential, functionally diverse non-protein-coding RNAs, raising the gene count by at least one order of magnitude. Most inherited phenotype-determining changes in DNA are in regulatory areas that control RNA and regulatory sequences. RNAs can directly or indirectly determine phenotypes by regulating protein and RNA function, transferring information within and between organisms, and generating DNA. RNAs also exhibit high structural, functional, and biomolecular interaction plasticity and are modified via editing, methylation, glycosylation, and other mechanisms, which bestow them with diverse intra- and extracellular functions without altering the underlying DNA. RNA is, therefore, currently considered the primary determinant of cellular to populational functional diversity, disease-linked and biomolecular structural variations, and cell function regulation. As demonstrated by RNA-based coronavirus vaccines' success, RNA technology is transforming medicine, agriculture, and industry, as did the advent of recombinant DNA technology in the 1980s.

Keywords

References

  1. Nat Commun. 2024 Feb 14;15(1):1365 [PMID: 38355719]
  2. Nat Rev Genet. 2021 Mar;22(3):185-198 [PMID: 33235359]
  3. Crit Rev Biochem Mol Biol. 2010 Oct;45(5):331-50 [PMID: 20572804]
  4. Nat Rev Genet. 2024 Oct;25(10):698-714 [PMID: 38605218]
  5. Nat Rev Genet. 2013 Mar;14(3):228-35 [PMID: 23416892]
  6. Genes Dev. 2023 May 1;37(9-10):354-376 [PMID: 37137715]
  7. Elife. 2021 May 04;10: [PMID: 33942720]
  8. RNA. 2023 Jul;29(7):865-884 [PMID: 37024263]
  9. Science. 2009 Oct 9;326(5950):289-93 [PMID: 19815776]
  10. Nature. 2024 Nov;635(8037):237-242 [PMID: 39385025]
  11. Nat Commun. 2014 Nov 25;5:5488 [PMID: 25421927]
  12. Nat Genet. 2008 Dec;40(12):1413-5 [PMID: 18978789]
  13. Cell Res. 2024 Sep;34(9):609-629 [PMID: 39054345]
  14. Symp Soc Exp Biol. 1958;12:138-63 [PMID: 13580867]
  15. Retrovirology. 2023 May 16;20(1):6 [PMID: 37194028]
  16. Noncoding RNA. 2020 Sep 17;6(3): [PMID: 32957640]
  17. Biochim Biophys Acta. 2008 Feb;1783(2):177-87 [PMID: 18068679]
  18. Science. 2024 Oct 4;386(6717):eadq3977 [PMID: 39208082]
  19. Nat Rev Mol Cell Biol. 2017 Jul;18(7):437-451 [PMID: 28488700]
  20. Theor Appl Genet. 2016 Dec;129(12):2267-2280 [PMID: 27717955]
  21. Genet Med. 2024 Sep 19;:101271 [PMID: 39305161]
  22. Nature. 2024 Oct;634(8035):986-994 [PMID: 39358506]
  23. Dev Cell. 2024 Apr 22;59(8):1058-1074.e11 [PMID: 38460509]
  24. Nat Commun. 2024 Mar 7;15(1):1781 [PMID: 38453932]
  25. RNA Biol. 2024 Jan;21(1):1-12 [PMID: 38091265]
  26. Annu Rev Cell Dev Biol. 2018 Oct 6;34:451-469 [PMID: 30028642]
  27. Genome Res. 2023 Dec 1;33(11):1865-1878 [PMID: 37945377]
  28. Mol Cell. 2021 Dec 2;81(23):4942-4953.e8 [PMID: 34655516]
  29. Cell. 2014 Dec 18;159(7):1665-80 [PMID: 25497547]
  30. Curr Top Microbiol Immunol. 1999;239:81-105 [PMID: 9893370]
  31. Viruses. 2009 Dec;1(3):1190-203 [PMID: 21994589]
  32. Cell Biosci. 2024 Sep 28;14(1):124 [PMID: 39342406]
  33. Front Microbiol. 2021 Oct 25;12:751880 [PMID: 34759902]
  34. Science. 2020 Aug 28;369(6507):1077-1084 [PMID: 32855333]
  35. Mol Biomed. 2023 Aug 24;4(1):25 [PMID: 37612540]
  36. Cell Prolif. 2022 Apr;55(4):e13202 [PMID: 35170113]
  37. Biol Direct. 2023 Mar 28;18(1):12 [PMID: 36978112]
  38. Exp Cell Res. 2020 Jun 1;391(1):111973 [PMID: 32209305]
  39. Nucleic Acids Res. 2021 Jan 8;49(D1):D916-D923 [PMID: 33270111]
  40. Nucleic Acids Res. 2014 Aug;42(14):8928-38 [PMID: 25013167]
  41. Hum Genet. 2016 Aug;135(8):851-67 [PMID: 27215579]
  42. Biochimie. 2011 Nov;93(11):1950-4 [PMID: 21824505]
  43. Nature. 1970 Aug 8;227(5258):561-3 [PMID: 4913914]
  44. Cancer Gene Ther. 2023 May;30(5):641-646 [PMID: 35136215]
  45. Nat Commun. 2018 Aug 27;9(1):3450 [PMID: 30150664]
  46. Trends Genet. 2013 Mar;29(3):176-86 [PMID: 23410786]
  47. Semin Cell Dev Biol. 2018 Mar;75:70-77 [PMID: 28866329]
  48. Hum Mol Genet. 2024 May 18;33(11):969-980 [PMID: 38483349]
  49. Front Mol Biosci. 2022 Sep 20;9:998363 [PMID: 36203874]
  50. Science. 2012 Dec 21;338(6114):1593-9 [PMID: 23258891]
  51. Nucleic Acids Res. 2018 Jan 9;46(1):314-323 [PMID: 29177466]
  52. Dev Cell. 2020 Oct 12;55(1):69-83 [PMID: 33049212]
  53. Nature. 2016 Oct 13;538(7624):265-269 [PMID: 27706140]
  54. Virology. 1998 Dec 20;252(2):287-303 [PMID: 9878607]
  55. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14984-9 [PMID: 23980164]
  56. Nature. 2012 Nov 1;491(7422):72-7 [PMID: 23075853]
  57. Nature. 2014 Jan 30;505(7485):696-700 [PMID: 24270811]
  58. Cell. 2024 Feb 15;187(4):846-860.e17 [PMID: 38262409]
  59. Mol Cell. 2024 Sep 19;84(18):3455-3468.e6 [PMID: 39208807]
  60. Nat Rev Genet. 2012 Jan 31;13(3):153-62 [PMID: 22290458]
  61. Science. 2024 May 24;384(6698):eadh7688 [PMID: 38781356]
  62. Proc Natl Acad Sci U S A. 2023 Feb 28;120(9):e2221529120 [PMID: 36812212]
  63. Cell. 1981 Dec;27(2 Pt 1):299-308 [PMID: 6277502]
  64. FEMS Microbiol Rev. 2021 Nov 23;45(6): [PMID: 33983378]
  65. Biomolecules. 2023 Mar 01;13(3): [PMID: 36979390]
  66. Front Mol Neurosci. 2018 Sep 05;11:311 [PMID: 30233312]
  67. Nat Commun. 2024 Oct 5;15(1):8637 [PMID: 39366968]
  68. Nat Commun. 2024 Jul 23;15(1):6187 [PMID: 39043684]
  69. Trends Microbiol. 2024 Apr;32(4):342-354 [PMID: 37802660]
  70. Nature. 1970 Jun 27;226(5252):1211-3 [PMID: 4316301]
  71. Exp Mol Med. 2024 Jun;56(6):1235-1249 [PMID: 38871819]
  72. J Autoimmun. 2001 May;16(3):293-302 [PMID: 11334495]
  73. Nature. 2024 Sep;633(8030):662-669 [PMID: 39261738]
  74. PLoS Genet. 2020 Oct 8;16(10):e1009034 [PMID: 33031395]
  75. Nat Commun. 2018 Jul 30;9(1):2973 [PMID: 30061690]
  76. Science. 2014 Feb 21;343(6173):875-7 [PMID: 24558158]
  77. Nat Neurosci. 2024 Jun;27(6):1051-1063 [PMID: 38594596]
  78. Nat Rev Mol Cell Biol. 2016 Apr;17(4):227-39 [PMID: 26726035]
  79. Cell. 2024 Sep 19;187(19):5228-5237.e12 [PMID: 39173631]
  80. Nature. 2023 Oct;622(7981):41-47 [PMID: 37794265]
  81. EMBO J. 2020 Mar 16;39(6):e102513 [PMID: 32073171]
  82. RNA Biol. 2021 Oct 15;18(sup1):51-60 [PMID: 34582322]
  83. Science. 2013 Oct 4;342(6154):118-23 [PMID: 24092744]
  84. Annu Rev Biochem. 2010;79:471-505 [PMID: 20235827]
  85. Sci Immunol. 2023 Nov 3;8(89):eadi8217 [PMID: 37922339]
  86. Nucleic Acids Res. 2009 Jul;37(12):3981-9 [PMID: 19406926]
  87. Nat Commun. 2017 Dec 18;8(1):2162 [PMID: 29255150]
  88. J Mol Biol. 1968 Dec;38(3):367-79 [PMID: 4887876]
  89. Nature. 2024 Jul;631(8020):432-438 [PMID: 38898279]
  90. Nat Struct Mol Biol. 2023 Oct;30(10):1525-1535 [PMID: 37710015]
  91. Nature. 2021 Oct;598(7880):359-363 [PMID: 34588692]
  92. Essays Biochem. 2020 Dec 7;64(6):883-894 [PMID: 33034351]
  93. PLoS Pathog. 2016 Jun 13;12(6):e1005672 [PMID: 27295279]
  94. Nature. 2008 Nov 27;456(7221):470-6 [PMID: 18978772]
  95. Nat Cell Biol. 2019 Feb;21(2):143-151 [PMID: 30602724]
  96. Nature. 1970 Jun 27;226(5252):1209-11 [PMID: 4316300]
  97. Front Cell Infect Microbiol. 2016 Jan 27;6:2 [PMID: 26858941]
  98. Mol Cell. 2024 Sep 5;84(17):3192-3208.e11 [PMID: 39173639]
  99. Science. 2024 Sep 20;385(6715):1278-1279 [PMID: 39298592]
  100. Mamm Genome. 2008 Aug;19(7-8):454-92 [PMID: 18839252]
  101. Genome Biol. 2014 Jun 30;15(6):R82 [PMID: 24981874]
  102. Cell. 2020 Dec 10;183(6):1551-1561.e12 [PMID: 33157039]
  103. J Biol Chem. 2007 Mar 9;282(10):7056-65 [PMID: 17213194]
  104. Proc Natl Acad Sci U S A. 2022 Oct 11;119(41):e2204636119 [PMID: 36197996]
  105. Nature. 2015 Feb 19;518(7539):317-30 [PMID: 25693563]
  106. Nature. 2019 Jul;571(7766):489-499 [PMID: 31341302]
  107. Nat Biotechnol. 2010 Aug;28(8):817-25 [PMID: 20657582]
  108. Sci Adv. 2022 Nov 25;8(47):eadd9938 [PMID: 36427315]
  109. Mol Cell. 2024 Oct 3;84(19):3810-3825.e10 [PMID: 39303720]
  110. Plant Sci. 2023 Oct;335:111822 [PMID: 37574140]
  111. Nat Rev Microbiol. 2019 Jan;17(2):110-123 [PMID: 30514982]
  112. Science. 2018 Jun 8;360(6393):1126-1129 [PMID: 29773668]
  113. Proc Natl Acad Sci U S A. 2022 Apr 26;119(17):e2112677119 [PMID: 35439059]
  114. Traffic. 2019 Nov;20(11):829-840 [PMID: 31513326]
  115. Nature. 1961 Dec 30;192:1227-32 [PMID: 13882203]
  116. Science. 2024 Oct 25;386(6720):eadj8172 [PMID: 39208083]
  117. Nat Rev Mol Cell Biol. 2018 Mar;19(3):158-174 [PMID: 29165424]
  118. Nat Cell Biol. 2007 Jun;9(6):654-9 [PMID: 17486113]
  119. Nat Methods. 2023 Jan;20(1):20-24 [PMID: 36635536]
  120. Mol Cell. 2022 Sep 1;82(17):3135-3150.e9 [PMID: 35914531]
  121. Anaerobe. 2024 Jun;87:102851 [PMID: 38583547]
  122. Nat Rev Mol Cell Biol. 2021 Mar;22(3):165-182 [PMID: 32873929]
  123. Trends Genet. 2012 Aug;28(8):409-16 [PMID: 22513408]
  124. Trends Genet. 2018 Aug;34(8):612-626 [PMID: 29908710]
  125. Cell. 2014 Mar 27;157(1):95-109 [PMID: 24679529]
  126. Curr Biol. 2017 Jul 24;27(14):R720-R730 [PMID: 28743023]
  127. Nat Commun. 2024 May 28;15(1):4285 [PMID: 38806455]
  128. RNA. 2004 Aug;10(8):1178-90 [PMID: 15272118]
  129. Annu Rev Genet. 2018 Nov 23;52:21-41 [PMID: 30160987]
  130. Q Rev Biol. 2009 Jun;84(2):131-76 [PMID: 19606595]
  131. Neuroscientist. 2023 Apr;29(2):166-176 [PMID: 34612730]
  132. Front Genet. 2017 Sep 20;8:125 [PMID: 28979293]
  133. J Mol Evol. 2023 Oct;91(5):570-580 [PMID: 37326679]
  134. Science. 2019 Aug 30;365(6456):919-922 [PMID: 31346137]
  135. Mol Cell. 2023 Mar 16;83(6):994-1011.e18 [PMID: 36806354]
  136. Sci Rep. 2024 Feb 29;14(1):5011 [PMID: 38424114]
  137. Genes Dev. 2024 Nov 27;38(21-24):979-997 [PMID: 39455282]
  138. Cold Spring Harb Perspect Med. 2015 Nov 02;5(11): [PMID: 26525452]
  139. Philos Trans A Math Phys Eng Sci. 2022 Jul 11;380(2227):20200422 [PMID: 35599566]
  140. Nat Commun. 2023 Dec 2;14(1):7991 [PMID: 38042949]
  141. N Engl J Med. 2021 Aug 12;385(7):658-660 [PMID: 34379930]
  142. Sci Adv. 2024 Jul 19;10(29):eado1218 [PMID: 39018396]
  143. Cold Spring Harb Symp Quant Biol. 1951;16:13-47 [PMID: 14942727]
  144. Sci Adv. 2019 Apr 10;5(4):eaaw1668 [PMID: 30989119]
  145. Science. 2024 Oct 4;386(6717):eadq0876 [PMID: 39116258]
  146. Mol Cell. 2021 Apr 15;81(8):1651-1665.e4 [PMID: 33705711]
  147. Annu Rev Microbiol. 1962;16:205-40 [PMID: 13931768]
  148. Nature. 2024 Mar;627(8004):671-679 [PMID: 38448585]
  149. Geroscience. 2022 Oct;44(5):2447-2459 [PMID: 36219280]
  150. Biophys J. 2014 Feb 18;106(4):955-65 [PMID: 24559998]
  151. Cell. 2019 Jan 10;176(1-2):56-72.e15 [PMID: 30612743]
  152. Cell. 2024 Aug 8;187(16):4193-4212.e24 [PMID: 38942014]
  153. mBio. 2022 Feb 8;13(1):e0356321 [PMID: 35132877]
  154. Signal Transduct Target Ther. 2024 Sep 16;9(1):232 [PMID: 39278916]
  155. Brain. 2022 Sep 14;145(9):2982-2990 [PMID: 36001414]
  156. Cell. 2021 Sep 30;184(20):5247-5260.e19 [PMID: 34534445]
  157. Nature. 2009 Nov 5;462(7269):58-64 [PMID: 19890323]
  158. Proc Natl Acad Sci U S A. 2024 Jul 16;121(29):e2404349121 [PMID: 38985764]
  159. Curr Opin Neurobiol. 2024 Jun;86:102876 [PMID: 38652980]
  160. Nat Rev Endocrinol. 2018 Jun;14(6):345-355 [PMID: 29666451]
  161. RSC Chem Biol. 2023 Jul 28;4(9):647-669 [PMID: 37654509]
  162. Nucleic Acids Res. 2023 Feb 22;51(3):1375-1392 [PMID: 36629268]
  163. Curr Biol. 2010 Sep 14;20(17):R754-63 [PMID: 20833320]
  164. Science. 2023 Sep 22;381(6664):eadd1250 [PMID: 37733848]
  165. Cell. 2023 Feb 16;186(4):715-731.e19 [PMID: 36754048]
  166. Genes (Basel). 2020 Nov 27;11(12): [PMID: 33261024]
  167. Retrovirology. 2006 Mar 17;3:18 [PMID: 16545126]
  168. Genome Biol. 2024 Sep 19;25(1):246 [PMID: 39300486]
  169. Nature. 2012 Apr 11;485(7398):376-80 [PMID: 22495300]
  170. Plants (Basel). 2024 Apr 18;13(8): [PMID: 38674546]
  171. EMBO J. 2010 Sep 15;29(18):3118-29 [PMID: 20717102]
  172. Nat Biotechnol. 2024 Apr;42(4):608-616 [PMID: 37217750]
  173. Trends Biochem Sci. 2003 Oct;28(10):521-3 [PMID: 14559179]
  174. Nat Neurosci. 2024 Jun;27(6):1087-1102 [PMID: 38600167]
  175. Genome Res. 2024 Nov 20;34(11):1774-1784 [PMID: 39472022]
  176. Curr Cancer Drug Targets. 2024;24(5):519-533 [PMID: 38804344]
  177. Cell Host Microbe. 2024 Jan 10;32(1):93-105.e6 [PMID: 38103543]
  178. Front Genet. 2022 Mar 23;13:832547 [PMID: 35401681]
  179. Nat Rev Genet. 2024 Nov;25(11):747 [PMID: 39294341]
  180. Nat Rev Mol Cell Biol. 2018 May;19(5):327-341 [PMID: 29339797]
  181. Nat Rev Mol Cell Biol. 2023 Apr;24(4):288-304 [PMID: 36424481]
  182. Viruses. 2024 Mar 20;16(3): [PMID: 38543832]
  183. Microbiol Spectr. 2018 Jul;6(4): [PMID: 30003865]
  184. Biomolecules. 2020 Sep 11;10(9): [PMID: 32932892]
  185. J Cell Sci. 2022 Jul 1;135(13): [PMID: 35788677]
  186. Adv Virus Res. 1972;17:295-313 [PMID: 4571739]
  187. Development. 2011 Sep;138(18):4075-84 [PMID: 21813571]
  188. Trends Neurosci. 2023 Jul;46(7):525-538 [PMID: 37202301]
  189. Int J Mol Sci. 2023 Apr 07;24(8): [PMID: 37108057]
  190. Front Med. 2024 Aug;18(4):622-648 [PMID: 38907157]
  191. Nature. 2023 Jul;619(7971):876-883 [PMID: 37468629]
  192. Nat Methods. 2024 Mar;21(3):411-422 [PMID: 38177506]
  193. Am J Hum Genet. 2018 Dec 6;103(6):1022-1029 [PMID: 30526861]
  194. Mol Cell. 2024 Aug 8;84(15):2838-2855.e10 [PMID: 39019045]
  195. Virus Evol. 2021 Mar 27;7(1):veab028 [PMID: 34141448]
  196. Plant Cell. 2023 May 29;35(6):1671-1707 [PMID: 36747354]
  197. Cell. 2017 Mar 23;169(1):13-23 [PMID: 28340338]
  198. Chem Rev. 2024 Mar 27;124(6):3186-3219 [PMID: 38466779]
  199. Nat Neurosci. 2024 Dec;27(12):2326-2340 [PMID: 39496796]
  200. Science. 1999 Mar 5;283(5407):1476-81 [PMID: 10066161]
  201. Nat Methods. 2023 May;20(5):673-676 [PMID: 37024650]
  202. Science. 2020 Apr 10;368(6487): [PMID: 32217750]
  203. Cell. 2021 Jun 10;184(12):3109-3124.e22 [PMID: 34004145]
  204. PLoS One. 2024 Sep 30;19(9):e0311120 [PMID: 39348365]
  205. PeerJ. 2018 Dec 18;6:e6136 [PMID: 30627482]

MeSH Term

Animals
Humans
Genome, Human
Molecular Biology
Phenotype
RNA

Chemicals

RNA

Word Cloud

Created with Highcharts 10.0.0RNADNARNAsgenomeprotein-codingsequencesgenesdeterminecentralmolecularbiologydogmainheritedconsidereddiverseregulatoryfunctionstructuralfunctionalbiomoleculartechnologyHumanprojects1990sidentified20000nowrevolutionpropelledrealizationphenotypebeyondfoundationalstatinglinearpiecestranscribedtranslatedproteinsCrucially95%initiallyjunkencodesessentialfunctionallynon-protein-codingraisinggenecountleastoneordermagnitudephenotype-determiningchangesareascontrolcandirectlyindirectlyphenotypesregulatingproteintransferringinformationwithinorganismsgeneratingalsoexhibithighinteractionplasticitymodifiedviaeditingmethylationglycosylationmechanismsbestowintra-extracellularfunctionswithoutalteringunderlyingthereforecurrentlyprimarydeterminantcellularpopulationaldiversitydisease-linkedvariationscellregulationdemonstratedRNA-basedcoronavirusvaccines'successtransformingmedicineagricultureindustryadventrecombinant1980sRevolutionCentralMolecularBiologyDogmaEvolutionmodificationsnoncoding

Similar Articles

Cited By