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Meiotic recombination hotspots of fission yeast are directed to loci that express non-coding RNA.

Wahls WP, Siegel ER, Davidson MK - PLoS ONE (2008)

Bottom Line: Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous.In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. wahlswaynep@uams.edu

ABSTRACT

Background: Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.

Methodology/principal findings: We compared the genome-wide distribution of DSB peaks to that of polyadenylated ncRNA molecules of the prl class. DSB peaks map to ncRNA loci that may be situated within ORFs, near the boundaries of ORFs and intergenic regions, or most often within intergenic regions. Unconditional statistical tests revealed that this colocalization is non-random and robust (P

Conclusions/significance: Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes.

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Colocalization of DSB hotspots with ncRNA.The frequencies of DSBs for each oligonucleotide tile (circles) and DSB peaks (curves) were plotted as a function of distance and are shown relative to the positions of protein-coding ORFs (boxes) and long ncRNAs (tos and prl, arrowhead indicates poly-A tail). The ncRNAs can be found within “weak” (C, I) and “prominent” (A, B, D–H) DSB peaks. Peaks and ncRNAs can map together within ORFs (A), near ORF-IGR boundaries (D, E), or within IGRs (B, C, F–I). The DSB-associated, polyadenylated ncRNAs may be spliced (H, I) or not (A–G).
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pone-0002887-g002: Colocalization of DSB hotspots with ncRNA.The frequencies of DSBs for each oligonucleotide tile (circles) and DSB peaks (curves) were plotted as a function of distance and are shown relative to the positions of protein-coding ORFs (boxes) and long ncRNAs (tos and prl, arrowhead indicates poly-A tail). The ncRNAs can be found within “weak” (C, I) and “prominent” (A, B, D–H) DSB peaks. Peaks and ncRNAs can map together within ORFs (A), near ORF-IGR boundaries (D, E), or within IGRs (B, C, F–I). The DSB-associated, polyadenylated ncRNAs may be spliced (H, I) or not (A–G).

Mentions: Our long-term interest is to define how meiotic homologous recombination becomes localized at hotspots. We therefore examined the genomic DNA sequences surrounding meiotic DSB peaks of fission yeast, and we discovered that several of the peaks encompass DNA sequences which express ncRNA molecules. For example, a prominent DSB peak within the rec7 gene encompasses three polyadenylated, transcript from opposite strand RNA molecules, tos1, tos2, and tos3 (Figure 2A). These non-coding tos transcripts are induced only in meiosis [38] and are therefore present when Rec12 (Spo11) catalyses the formation of DSBs. Similarly, some prominent DSB peaks contain prl transcripts (polyA-bearing RNA without long open reading frames [5]) (e.g., Figure 2B). Such non-coding prl transcripts are expressed in meiosis, are found within both coding regions and IGRs but localize preferentially to large IGRs, and some of them are spliced [5], [39]. In other words, the distribution and developmental regulation of some polyadenylated, ncRNA molecules seem to coincide with those of prominent DSB peaks.


Meiotic recombination hotspots of fission yeast are directed to loci that express non-coding RNA.

Wahls WP, Siegel ER, Davidson MK - PLoS ONE (2008)

Colocalization of DSB hotspots with ncRNA.The frequencies of DSBs for each oligonucleotide tile (circles) and DSB peaks (curves) were plotted as a function of distance and are shown relative to the positions of protein-coding ORFs (boxes) and long ncRNAs (tos and prl, arrowhead indicates poly-A tail). The ncRNAs can be found within “weak” (C, I) and “prominent” (A, B, D–H) DSB peaks. Peaks and ncRNAs can map together within ORFs (A), near ORF-IGR boundaries (D, E), or within IGRs (B, C, F–I). The DSB-associated, polyadenylated ncRNAs may be spliced (H, I) or not (A–G).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2483352&req=5

pone-0002887-g002: Colocalization of DSB hotspots with ncRNA.The frequencies of DSBs for each oligonucleotide tile (circles) and DSB peaks (curves) were plotted as a function of distance and are shown relative to the positions of protein-coding ORFs (boxes) and long ncRNAs (tos and prl, arrowhead indicates poly-A tail). The ncRNAs can be found within “weak” (C, I) and “prominent” (A, B, D–H) DSB peaks. Peaks and ncRNAs can map together within ORFs (A), near ORF-IGR boundaries (D, E), or within IGRs (B, C, F–I). The DSB-associated, polyadenylated ncRNAs may be spliced (H, I) or not (A–G).
Mentions: Our long-term interest is to define how meiotic homologous recombination becomes localized at hotspots. We therefore examined the genomic DNA sequences surrounding meiotic DSB peaks of fission yeast, and we discovered that several of the peaks encompass DNA sequences which express ncRNA molecules. For example, a prominent DSB peak within the rec7 gene encompasses three polyadenylated, transcript from opposite strand RNA molecules, tos1, tos2, and tos3 (Figure 2A). These non-coding tos transcripts are induced only in meiosis [38] and are therefore present when Rec12 (Spo11) catalyses the formation of DSBs. Similarly, some prominent DSB peaks contain prl transcripts (polyA-bearing RNA without long open reading frames [5]) (e.g., Figure 2B). Such non-coding prl transcripts are expressed in meiosis, are found within both coding regions and IGRs but localize preferentially to large IGRs, and some of them are spliced [5], [39]. In other words, the distribution and developmental regulation of some polyadenylated, ncRNA molecules seem to coincide with those of prominent DSB peaks.

Bottom Line: Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous.In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America. wahlswaynep@uams.edu

ABSTRACT

Background: Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.

Methodology/principal findings: We compared the genome-wide distribution of DSB peaks to that of polyadenylated ncRNA molecules of the prl class. DSB peaks map to ncRNA loci that may be situated within ORFs, near the boundaries of ORFs and intergenic regions, or most often within intergenic regions. Unconditional statistical tests revealed that this colocalization is non-random and robust (P

Conclusions/significance: Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes.

Show MeSH
Related in: MedlinePlus