Cargando…

The evolution of core proteins involved in microRNA biogenesis

BACKGROUND: MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs (ncRNAs) which play important roles in eukaryotic gene regulation. miRNA biogenesis and activation is a complex process involving multiple protein catalysts and involves the large macromolecular RNAi Silencing Complex...

Descripción completa

Detalles Bibliográficos
Autores principales: Murphy, Dennis, Dancis, Barry, Brown, James R
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287173/
https://www.ncbi.nlm.nih.gov/pubmed/18366743
http://dx.doi.org/10.1186/1471-2148-8-92
_version_ 1782152075210129408
author Murphy, Dennis
Dancis, Barry
Brown, James R
author_facet Murphy, Dennis
Dancis, Barry
Brown, James R
author_sort Murphy, Dennis
collection PubMed
description BACKGROUND: MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs (ncRNAs) which play important roles in eukaryotic gene regulation. miRNA biogenesis and activation is a complex process involving multiple protein catalysts and involves the large macromolecular RNAi Silencing Complex or RISC. While phylogenetic analyses of miRNA genes have been previously published, the evolution of miRNA biogenesis itself has been little studied. In order to better understand the origin of miRNA processing in animals and plants, we determined the phyletic occurrences and evolutionary relationships of four major miRNA pathway protein components; Dicer, Argonaute, RISC RNA-binding proteins, and Exportin-5. RESULTS: Phylogenetic analyses show that all four miRNA pathway proteins were derived from large multiple protein families. As an example, vertebrate and invertebrate Argonaute (Ago) proteins diverged from a larger family of PIWI/Argonaute proteins found throughout eukaryotes. Further gene duplications among vertebrates after the evolution of chordates from urochordates but prior to the emergence of fishes lead to the evolution of four Ago paralogues. Invertebrate RISC RNA-binding proteins R2D2 and Loquacious are related to other RNA-binding protein families such as Staufens as well as vertebrate-specific TAR (HIV trans-activator RNA) RNA-binding protein (TRBP) and protein kinase R-activating protein (PACT). Export of small RNAs from the nucleus, including miRNA, is facilitated by three closely related karyopherin-related nuclear transporters, Exportin-5, Exportin-1 and Exportin-T. While all three exportins have direct orthologues in deutrostomes, missing exportins in arthropods (Exportin-T) and nematodes (Exportin-5) are likely compensated by dual specificities of one of the other exportin paralogues. CONCLUSION: Co-opting particular isoforms from large, diverse protein families seems to be a common theme in the evolution of miRNA biogenesis. Human miRNA biogenesis proteins have direct, orthologues in cold-blooded fishes and, in some cases, urochordates and deutrostomes. However, lineage specific expansions of Dicer in plants and invertebrates as well as Argonaute and RNA-binding proteins in vertebrates suggests that novel ncRNA regulatory mechanisms can evolve in relatively short evolutionary timeframes. The occurrence of multiple homologues to RNA-binding and Argonaute/PIWI proteins also suggests the possible existence of further pathways for additional types of ncRNAs.
format Text
id pubmed-2287173
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-22871732008-04-04 The evolution of core proteins involved in microRNA biogenesis Murphy, Dennis Dancis, Barry Brown, James R BMC Evol Biol Research Article BACKGROUND: MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs (ncRNAs) which play important roles in eukaryotic gene regulation. miRNA biogenesis and activation is a complex process involving multiple protein catalysts and involves the large macromolecular RNAi Silencing Complex or RISC. While phylogenetic analyses of miRNA genes have been previously published, the evolution of miRNA biogenesis itself has been little studied. In order to better understand the origin of miRNA processing in animals and plants, we determined the phyletic occurrences and evolutionary relationships of four major miRNA pathway protein components; Dicer, Argonaute, RISC RNA-binding proteins, and Exportin-5. RESULTS: Phylogenetic analyses show that all four miRNA pathway proteins were derived from large multiple protein families. As an example, vertebrate and invertebrate Argonaute (Ago) proteins diverged from a larger family of PIWI/Argonaute proteins found throughout eukaryotes. Further gene duplications among vertebrates after the evolution of chordates from urochordates but prior to the emergence of fishes lead to the evolution of four Ago paralogues. Invertebrate RISC RNA-binding proteins R2D2 and Loquacious are related to other RNA-binding protein families such as Staufens as well as vertebrate-specific TAR (HIV trans-activator RNA) RNA-binding protein (TRBP) and protein kinase R-activating protein (PACT). Export of small RNAs from the nucleus, including miRNA, is facilitated by three closely related karyopherin-related nuclear transporters, Exportin-5, Exportin-1 and Exportin-T. While all three exportins have direct orthologues in deutrostomes, missing exportins in arthropods (Exportin-T) and nematodes (Exportin-5) are likely compensated by dual specificities of one of the other exportin paralogues. CONCLUSION: Co-opting particular isoforms from large, diverse protein families seems to be a common theme in the evolution of miRNA biogenesis. Human miRNA biogenesis proteins have direct, orthologues in cold-blooded fishes and, in some cases, urochordates and deutrostomes. However, lineage specific expansions of Dicer in plants and invertebrates as well as Argonaute and RNA-binding proteins in vertebrates suggests that novel ncRNA regulatory mechanisms can evolve in relatively short evolutionary timeframes. The occurrence of multiple homologues to RNA-binding and Argonaute/PIWI proteins also suggests the possible existence of further pathways for additional types of ncRNAs. BioMed Central 2008-03-25 /pmc/articles/PMC2287173/ /pubmed/18366743 http://dx.doi.org/10.1186/1471-2148-8-92 Text en Copyright ©2008 Murphy et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Murphy, Dennis
Dancis, Barry
Brown, James R
The evolution of core proteins involved in microRNA biogenesis
title The evolution of core proteins involved in microRNA biogenesis
title_full The evolution of core proteins involved in microRNA biogenesis
title_fullStr The evolution of core proteins involved in microRNA biogenesis
title_full_unstemmed The evolution of core proteins involved in microRNA biogenesis
title_short The evolution of core proteins involved in microRNA biogenesis
title_sort evolution of core proteins involved in microrna biogenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2287173/
https://www.ncbi.nlm.nih.gov/pubmed/18366743
http://dx.doi.org/10.1186/1471-2148-8-92
work_keys_str_mv AT murphydennis theevolutionofcoreproteinsinvolvedinmicrornabiogenesis
AT dancisbarry theevolutionofcoreproteinsinvolvedinmicrornabiogenesis
AT brownjamesr theevolutionofcoreproteinsinvolvedinmicrornabiogenesis
AT murphydennis evolutionofcoreproteinsinvolvedinmicrornabiogenesis
AT dancisbarry evolutionofcoreproteinsinvolvedinmicrornabiogenesis
AT brownjamesr evolutionofcoreproteinsinvolvedinmicrornabiogenesis