Cargando…

The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis

PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements(1). piRNA populations comprise a molecular definition of transposons th...

Descripción completa

Detalles Bibliográficos
Autores principales: Ipsaro, Jonathan J., Haase, Astrid D., Knott, Simon R., Joshua-Tor, Leemor, Hannon, Gregory J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493678/
https://www.ncbi.nlm.nih.gov/pubmed/23064227
http://dx.doi.org/10.1038/nature11502
_version_ 1782249308506030080
author Ipsaro, Jonathan J.
Haase, Astrid D.
Knott, Simon R.
Joshua-Tor, Leemor
Hannon, Gregory J.
author_facet Ipsaro, Jonathan J.
Haase, Astrid D.
Knott, Simon R.
Joshua-Tor, Leemor
Hannon, Gregory J.
author_sort Ipsaro, Jonathan J.
collection PubMed
description PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements(1). piRNA populations comprise a molecular definition of transposons that permits them to be distinguished from host genes and selectively silenced. piRNAs can be generated in two distinct ways. Primary piRNAs emanate from discrete genomic loci, termed piRNA clusters, and appear to be derived from long, single-stranded precursors(2). The biogenesis of primary piRNAs involves at least two nucleolytic steps. An unknown enzyme cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5' ends. piRNA 3' ends are likely formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner(1,3). Secondary piRNAs arise during the adaptive ping-pong cycle, with their 5' termini being formed by the activity of PIWIs themselves(2,4). A number of proteins have been implicated genetically in primary piRNA biogenesis. One of these, Zucchini, is a member of the phospholipase D family of phosphodiesterases, which includes both phospholipases and nucleases(5–7). We have produced a dimeric, soluble fragment of the mouse Zucchini homolog (mZuc/PLD6) and have shown that it possesses single strand-specific nuclease activity. A crystal structure of mZuc at 1.75 Å resolution indicates greater architectural similarity to PLD-family nucleases than to phospholipases. Considered together, our data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5' ends of primary piRNAs.
format Online
Article
Text
id pubmed-3493678
institution National Center for Biotechnology Information
language English
publishDate 2012
record_format MEDLINE/PubMed
spelling pubmed-34936782013-05-08 The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis Ipsaro, Jonathan J. Haase, Astrid D. Knott, Simon R. Joshua-Tor, Leemor Hannon, Gregory J. Nature Article PIWI-family proteins and their associated small RNAs (piRNAs) act in an evolutionarily conserved innate immune mechanism that provides an essential protection for germ cell genomes against the activity of mobile genetic elements(1). piRNA populations comprise a molecular definition of transposons that permits them to be distinguished from host genes and selectively silenced. piRNAs can be generated in two distinct ways. Primary piRNAs emanate from discrete genomic loci, termed piRNA clusters, and appear to be derived from long, single-stranded precursors(2). The biogenesis of primary piRNAs involves at least two nucleolytic steps. An unknown enzyme cleaves piRNA cluster transcripts to generate monophosphorylated piRNA 5' ends. piRNA 3' ends are likely formed by exonucleolytic trimming, after a piRNA precursor is loaded into its PIWI partner(1,3). Secondary piRNAs arise during the adaptive ping-pong cycle, with their 5' termini being formed by the activity of PIWIs themselves(2,4). A number of proteins have been implicated genetically in primary piRNA biogenesis. One of these, Zucchini, is a member of the phospholipase D family of phosphodiesterases, which includes both phospholipases and nucleases(5–7). We have produced a dimeric, soluble fragment of the mouse Zucchini homolog (mZuc/PLD6) and have shown that it possesses single strand-specific nuclease activity. A crystal structure of mZuc at 1.75 Å resolution indicates greater architectural similarity to PLD-family nucleases than to phospholipases. Considered together, our data suggest that the Zucchini proteins act in primary piRNA biogenesis as nucleases, perhaps generating the 5' ends of primary piRNAs. 2012-10-14 2012-11-08 /pmc/articles/PMC3493678/ /pubmed/23064227 http://dx.doi.org/10.1038/nature11502 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ipsaro, Jonathan J.
Haase, Astrid D.
Knott, Simon R.
Joshua-Tor, Leemor
Hannon, Gregory J.
The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title_full The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title_fullStr The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title_full_unstemmed The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title_short The structural biochemistry of Zucchini implicates it as a nuclease in piRNA biogenesis
title_sort structural biochemistry of zucchini implicates it as a nuclease in pirna biogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493678/
https://www.ncbi.nlm.nih.gov/pubmed/23064227
http://dx.doi.org/10.1038/nature11502
work_keys_str_mv AT ipsarojonathanj thestructuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT haaseastridd thestructuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT knottsimonr thestructuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT joshuatorleemor thestructuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT hannongregoryj thestructuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT ipsarojonathanj structuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT haaseastridd structuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT knottsimonr structuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT joshuatorleemor structuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis
AT hannongregoryj structuralbiochemistryofzucchiniimplicatesitasanucleaseinpirnabiogenesis