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Target-dependent siRNA suppression distinguishes self from non-self endogenous siRNAs in C. elegans germline

Zoran Gajic, Diljeet Kaur, Julie Ni, Zhaorong Zhu, Anna Zhebrun, Maria Gajic, Matthew Kim, Julia Hong, Monika Priyadarshini, Christian Frøkjær-Jensen, Sam Gu
doi: https://doi.org/10.1101/2022.01.25.477739
Zoran Gajic
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
3Vilcek Institute of Graduate Biomedical Sciences, NYU Langone Health, New York, NY, 10010, USA
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Diljeet Kaur
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
4Genetics and Epigenetics Program, The University of Pennsylvania, Philadelphia, PA 19104, USA
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Julie Ni
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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Zhaorong Zhu
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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Anna Zhebrun
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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Maria Gajic
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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Matthew Kim
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
5University of Pennsylvania, Philadelphia, PA 19104, USA
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Julia Hong
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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Monika Priyadarshini
6Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955–6900, Kingdom of Saudi Arabia
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Christian Frøkjær-Jensen
6Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955–6900, Kingdom of Saudi Arabia
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Sam Gu
2Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
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  • For correspondence: sam.gu@rutgers.edu
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Abstract

Despite their prominent role in transposon silencing, expression of endo-siRNAs is not limited to the “non-self” DNA elements. Transcripts of protein-coding genes (“self” DNA) in some cases also produce endo-siRNAs in yeast, plants, and animals [1]. How cells distinguish these two populations of siRNAs to prevent unwanted silencing of self-genes in animals is not well understood. To address this question, we examined the expression of ectopic siRNAs from an LTR retrotransposon in C. elegans germline. We found that the abundance of ectopic siRNAs was dependent on their homologous target genes: ectopic siRNAs against genes expressed only in somatic cells can be abundantly expressed. In contrast, ectopic siRNAs against germline-expressed genes are often suppressed. This phenomenon, which we termed “target-directed siRNA suppression”, is dependent on the target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur to naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 26, 2022.
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Target-dependent siRNA suppression distinguishes self from non-self endogenous siRNAs in C. elegans germline
Zoran Gajic, Diljeet Kaur, Julie Ni, Zhaorong Zhu, Anna Zhebrun, Maria Gajic, Matthew Kim, Julia Hong, Monika Priyadarshini, Christian Frøkjær-Jensen, Sam Gu
bioRxiv 2022.01.25.477739; doi: https://doi.org/10.1101/2022.01.25.477739
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Target-dependent siRNA suppression distinguishes self from non-self endogenous siRNAs in C. elegans germline
Zoran Gajic, Diljeet Kaur, Julie Ni, Zhaorong Zhu, Anna Zhebrun, Maria Gajic, Matthew Kim, Julia Hong, Monika Priyadarshini, Christian Frøkjær-Jensen, Sam Gu
bioRxiv 2022.01.25.477739; doi: https://doi.org/10.1101/2022.01.25.477739

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