Dicer has long been known for its ability to produce siRNAs and miRNAs, the guides which drive RNA silencing, from long, double-stranded RNA or miRNA precursors (pre-miRNAs). Kaneko et al. now report a fascinating role for mammalian Dicer, separate from its function in RNA silencing.

In a series of elegant experiments, the authors show a role for mammalian Dicer in preventing the inflammatory changes of geographic atrophy or “dry” age related macular degeneration (AMD) by degrading Alu dsRNA in the retinal pigmented epithelial (RPE) cells of both mice and humans. Interestingly, this effect was due to the endonuclease activity of Dicer alone
degrading dsRNA, independent of siRNA loading in the RNA-induced silencing complex (RISC).

They …

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High throughput sequencing has broadened our understanding of countless biological processes and led to scientific advancements in  clinical therapeutics.   With massively parallel sequencing becoming a staple in laboratories worldwide, we need to understand the  limitations and biases of the technology. PCR amplification is an essential step in the preparation of a library for high throughput  sequencing.  However, biases introduced by PCR, reflecting the GC content and length of the template, can have detrimental effects on library generation. 

Dabney and Meyer have now compared ten commercially available PCR polymerase-buffer systems (Dabney and Meyer, Biotechniques 52:87-94, 2012) to determine the biases they introduce in sequencing both modern and ancient DNA.  For modern DNA library  preparation, Herculase II Fusion polymerase …

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Silence is inviting submissions for a new article series on methods and protocols in analyzing RNA.

This special collection of articles will provide novel insights into the latest methods within the field of RNA, addressing questions of general interest to the RNA community, as well as predictions on future uses, modifications and improvements that would advance existing methods beyond their current use.

To submit your manuscript, please use our online submission system and indicate in your covering letter that you would like it to be considered for the series, or alternatively, send a pre-submission enquiry to editorial@silencejournal.com.

It has been more than a decade since Dicer was identified as the siRNA and miRNA-generating enzyme. Dicer proteins exist in nearly all eukaryotes and are well know for their ability to convert long, double-stranded RNA, or miRNA precursors  (pre-miRNAs) into 21-23 nt long duplexes. Therefore, Dicer has been dubbed a ‘molecular ruler.’

In Drosophila melanogaster there are two Dicer proteins. Dicer-2—along with its partner R2D2 — processes long, double-stranded RNA; whereas Dicer-1 cleaves miRNA precursors—stem-loop RNAs ∼70 nt long. What restricts Dicer-1 to processes primarily pre-miRNA into and not long double-stranded RNA?

Using classical biochemistry, Tsutsumi et al. (doi:10.1038/nsmb.2125) now show that fly Dicer-1 recognizes the single-stranded terminal loop of pre-miRNA through the Dicer-1 helicase domain, sensing terminal loop …

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We are delighted to announce the appointment of Yijun Qi to co-Editor-in-Chief of Silence, alongside Phillip Zamore.

Yijun is currently an Associate Investigator at the National Institute of Biological Sciences in Beijing, and his research focuses on dissecting the mechanisms of RNAi pathways and the biological functions of small RNAs in plants.

His lab has discovered miRNAs in single-celled green algae, identified a novel class of long miRNAs that direct DNA methylation, and provided insights into how small RNAs are sorted into plant Argonaute complexes.

Currently, transgenic flies expressing long inverted repeat transcripts that generate double-stranded RNA are available for nearly every Drosophila gene, allowing genome-wide RNAi screening. However, long double-stranded RNA does not  efficiently trigger RNAi in the ovary germline. To achieve effective RNAi in the female germline, Ni et al. (Ni et al., Nature Methods 8, 405-407, 2011) systematically tested the efficiency of artificial microRNA precursors (shRNAs) to silence specific genes in the germline. The result of their studies was Valium22, a vector that combines optimized germline-specific expression promoter sequences with a modified backbone from pre-miR-1. They evaluated this construct by generating shRNA transgenic flies targeting four piRNA pathway genes. The RNAi phenotypes from each Valium22 line phenocopied the corresponding null mutants. …

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In a recent issue of Nature, Lin et al. {Lin et al., 2011, Nature, 469, 559-63}  reported the structure of box C/D ribonucleoprotein (RNP) in complex with its substrate, highlighting the mechanism behind site-specific ribose methylation. Box C/D RNP and H/ACA RNP belong to the small nucleolar RNP (snoRNP) family that methylates and pseudouridylates  pre-rRNA respectively. In addition, the founding member of the family, U3 snoRNP, cleaves and liberates rRNA for ribosome assembly {Maxwell and Fournier, 1995, Annu Rev Biochem, 64, 897-934}. Intriguingly, the study by Lin et al. reveals that box C/D methylation bears some resemblance to RNA interference (RNAi), where sequence specific base pairing between RNA guide and substrate acts as the molecular ruler: the site of …

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During meiotic prophase, homologous chromosomes must pair (synapse) in order to be separated appropriately during the first meiotic division. It is believed that meiotic sex chromosome inactivation (MSCI) evolves to mask the sex chromosome asynapsis for the heterogametic sex with distinctive heteromorphic sex chromosomes. It is has been shown that during pachytene stage, almost all the protein coding genes on the sex chromosomes are silenced. However, a study from the Yan lab (Song et al.) has found that many X-linked miRNAs are transcribed by Pol II at the pachytene stage, suggesting that mechanisms of MSCI may be different from conventional heterochromatin silencing, and the miRNA on sex chromosomes may undergo distinct regulation. It would be interesting to …

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In an article recently published in Silence, Earley et al. describe how loss-of-function mutations in the F-box-gene FBW2 serve to increase the protein levels of ARGONAUTE1 (AGO1), a core component of the RNA-induced silencing complex in Arabidopsis thaliana.

Conversely, over-expression of the endogenous F-box protein leads to a decrease in the abundance of AGO1 protein levels, but not AGO1 mRNA. Together, these results indicate the novel role of FBW2 as a negative regulator of AGO1 protein levels, contributing yet another layer of complexity to the mechanisms involved in AGO1 homeostasis.

Although FBW2 mutants possess no obvious morphological phenotype, they do display a reduced sensitivity to the plant growth regulator abscisic acid (ABA), suggesting that FBW2 may also play a role …

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David Baulcombe and Phillip Zamore are very happy to announce the addition of Olivier Voinnet to Silence as Senior Editor.

Currently a senior researcher at the CNRS Institute of Plant Molecular Biology in Strasbourg, Voinnet  gained his PhD in David Baulcome’s lab in 2001, before establishing his own lab in 2002.

In 2009, he was awarded an EMBO Gold Medal for his pioneering work on the mechanisms and roles of RNA silencing in plants.