Effects of G-quadruplex topology on translational inhibition by tRNA fragments in mammalian and plant systems in vitro

Jackowiak, Paulina; Hojka-Osińska, Anna; Gasiorek, Katarzyna; Stelmaszczuk, Michal; Gudanis, Dorota; Gdaniec, Zofia; Figlerowicz, Marek

doi:10.1016/j.biocel.2017.10.001

Cited by 15 publications

(8 citation statements)

References 35 publications

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“…A similar role has already been proposed for another type of RNA structure recognized by Dicer, i.e., RNA hairpins formed within endogenous transcripts [32] or adopted by viral RNAs [36]. Short RNAs, including miRNAs [37], piRNAs [38], and tRNA fragments [39,40], can adopt G-quadruplex structures. The length of these RNAs (~20-30 nt) is close to the length of the guanine-rich oligonucleotides used in the present study (10-22 nt).…”

Section: Discussionsupporting

confidence: 57%

RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity

Koralewska

Szczepańska

Ciechanowska

et al. 2021

Cell. Mol. Life Sci.

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Guanine (G)-rich single-stranded nucleic acids can adopt G-quadruplex structures. Accumulating evidence indicates that G-quadruplexes serve important regulatory roles in fundamental biological processes such as DNA replication, transcription, and translation, while aberrant G-quadruplex formation is linked to genome instability and cancer. Understanding the biological functions played by G-quadruplexes requires detailed knowledge of their protein interactome. Here, we report that both RNA and DNA G-quadruplexes are bound by human Dicer in vitro. Using in vitro binding assays, mutation studies, and computational modeling we demonstrate that G-quadruplexes can interact with the Platform–PAZ–Connector helix cassette of Dicer, the region responsible for anchoring microRNA precursors (pre-miRNAs). Consequently, we show that G-quadruplexes efficiently and stably inhibit the cleavage of pre-miRNA by Dicer. Our data highlight the potential of human Dicer for binding of G-quadruplexes and allow us to propose a G-quadruplex-driven sequestration mechanism of Dicer regulation.

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Section: Discussionsupporting

confidence: 57%

RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity

Koralewska

Szczepańska

Ciechanowska

et al. 2021

Cell. Mol. Life Sci.

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“…Experimental evidence for G4 function in plants remains rather sparse. Already reported examples include 5′UTR G4 acting as a repressor of translation (Kwok et al, 2015) and G4s located within tRNA-derived fragments (tRFs) acting as a mild modulator of translation efficiency in vitro (Jackowiak et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Sequence Dynamics of Pre-mRNA G-Quadruplexes in Plants

Kopec

Karłowski

2019

Front. Plant Sci.

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Intramolecular G-quadruplexes (G4s) are secondary structures that may form within G-rich stretches of nucleic acids. Although their presence has been associated with genomic instability and mutagenicity, recent reports suggest their involvement in regulation of diverse cellular events, including transcription and translation. The majority of data regarding G4s stems from mammalian and yeast studies, leaving the plant G4s almost unexplored. Using the publicly available Arabidopsis thaliana and Oryza sativa WGS data, we examined the single nucleotide variability of sequences predicted to form G4s (pG4s) structures. We focused our analysis on protein coding transcripts and compared the results to well-characterized Homo sapiens data. We demonstrate that the overall high variability of pG4s is not uniform and differs between gene structural elements. Specifically, plant AUG-containing pG4s, located within 5′UTR/CDS junctions, are abundant and appear not to be affected by a higher frequency of sequence change, indicating their functional relevance. Furthermore, we show that substitutions lowering the probability of G4s’ formation are preferred over neutral or stabilizing modifications.

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“…A similar role has already been proposed for another type of RNA structure recognized by Dicer, i.e., RNA hairpins formed within endogenous transcripts (32) or adopted by viral RNAs (36). Short RNAs, including miRNAs (37), piRNAs (38), and tRNA fragments (39, 40), can adopt G-quadruplex structures. The length of these RNAs (∼20-30 nt) is close to the length of the guanine-rich oligonucleotides used in the present study (10-22 nt).…”

Section: Discussionmentioning

confidence: 99%

RNA and DNA G-quadruplexes bind to human Dicer and inhibit its activity

Koralewska

Szczepańska

Ciechanowska

et al. 2020

Preprint

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Guanine (G)-rich single-stranded nucleic acids can adopt G-quadruplex structures. Accumulating evidence indicates that G-quadruplexes serve important regulatory roles in fundamental biological processes such as DNA replication, transcription, and translation, while aberrant G-quadruplex formation is linked to genome instability and cancer. Understanding the biological functions played by G-quadruplexes requires detailed knowledge of their protein interactome. Here, we report that both RNA and DNA G-quadruplexes are bound by human Dicer in vitro. Using in vitro binding assays, mutation studies, and computational modeling we demonstrate that Gquadruplexes can interact with the Platform-PAZ-Connector helix cassette of Dicer, the region responsible for anchoring microRNA precursors (pre-miRNAs). Consequently, we show that Gquadruplexes efficiently and stably inhibit the cleavage of pre-miRNA by Dicer. Our data highlight the potential of human Dicer for binding of G-quadruplexes and allow us to propose a Gquadruplex-driven sequestration mechanism of Dicer regulation. Main Text

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Effects of G-quadruplex topology on translational inhibition by tRNA fragments in mammalian and plant systems in vitro

Cited by 15 publications

References 35 publications

RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity

RNA and DNA G-quadruplexes bind to human dicer and inhibit its activity

Sequence Dynamics of Pre-mRNA G-Quadruplexes in Plants

RNA and DNA G-quadruplexes bind to human Dicer and inhibit its activity

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