Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs.

By Joshua Babiarz, J. Ruby, Yangming Wang, David P. Bartel, Robert Blelloch. Genes & Development, 2008

945 citations recorded by the source corpus.

Canonical microRNAs (miRNAs) require two processing steps: the first by the Microprocessor, a complex of DGCR8 and Drosha, and the second by a complex of TRBP and Dicer. dgcr8Delta/Delta mouse embryonic stem cells (mESCs) have less severe phenotypes than dicer1Delta/Delta mESCs, suggesting a physiological role for Microprocessor-independent, Dicer-dependent small RNAs. To identify these small RNAs with unusual biogenesis, we performed high-throughput sequencing from wild-type, dgcr8Delta/Delta, and dicer1Delta/Delta mESCs. Several of the resulting DGCR8-independent, Dicer-dependent RNAs were noncanonical miRNAs. These derived from mirtrons and a newly identified subclass of miRNA precursors, which appears to be the endogenous counterpart of shRNAs. Our analyses also revealed endogenous siRNAs resulting from Dicer cleavage of long hairpins, the vast majority of which originated from one genomic locus with tandem, inverted short interspersed nuclear elements (SINEs). Our results extend the known diversity of mammalian small RNA-generating pathways and show that mammalian siRNAs exist in cell types other than oocytes.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a3e9b6f13f8d590742d03bfaec4da81d220b5cf4

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Citations in the corpus

An overview of microRNAs (2015, background): “The most common variation is the mirtron class of miRNAs[80-83].”
Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. (2009, methodology): “The common feature of these siRNAs is that their processing is not dependent on Drosha and DGCR8 (Babiarz et al. 2008; Ghildiyal et al. 2008).”
Metazoan MicroRNAs (2018, background): “However, for the best-characterized cellular endogenous shRNAs, which are Pol II products, the transcription start site defines the 5′ terminus of the Dicer substrate, and maturation of the 3′ terminus, although known to be Drosha-independent, is uncharacterized (Babiarz et al., 2008; Xie et al., 20”
Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. (2010, methodology): “Although mmu-miR-1839, an annotated shRNA (Babiarz et al. 2008), did not overexpress, mmumiR-344e and mmu-miR-344f, novel shRNAs, did overexpress from our vector, and, as expected for shRNAs, their biogenesis was Drosha-independent (Fig.”
MicroRNAs in human cancer. (2013, background): “DGCR8 and RNASEN independent miRNAs include mirtrons and tailed mirtrons, which release their pre-miRNA by splicing and exonuclase trimming [80, 81].”
Human tRNA-derived small RNAs in the global regulation of RNA silencing. (2010, background): “Importantly, the abundance of cand45 itself was not affected by Argonaute overexpressions, as was the case for microRNAs 20 and 21 and the bioinformatically predicted endo-shRNAs 320 and 484 (Babiarz et al. 2008), arguing that these are already efficiently incorporated into Argonautes at physiologic”
Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. (2016, background): “Furthermore, pre-miRNAs can be derived from small nucleolar RNAs (snoRNAs) (69) or tRNA precursors (9).”
Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018, background): “An example of such pre-miRNAs is mirtrons, which are produced from the introns of mRNA during splicing (35, 36).”
tRNA biology charges to the front. (2010, background): “Deep sequencing has revealed the existence of a prominent Dicer-generated tRNA fragment in mouse embryonic stem (ES) cells that derives from the 39 end of the gene and part of the trailer sequence, and may arise because of alternative folding of the tRNA transcript (Babiarz et al. 2008).”