Showing papers by "Amy E. Pasquinelli published in 2019"
TL;DR: These findings highlight the importance of sequences beyond the seed in controlling the function and existence of miRNAs and the extent of pairing to the miRNA 3' end can influence the stability of the mi RNA itself.
162 citations
TL;DR: The understanding of poly(A) tail length has evolved over the past 5 years with the recognition that highly expressed genes can have short poly( a) tails and the elucidation of the seemingly contradictory roles for poly( A)-binding protein (PABP) in facilitating both protection and deadenylation.
113 citations
TL;DR: These studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR.
Abstract: Heat Shock Factor 1 (HSF-1) is a key regulator of the heat shock response (HSR). Upon heat shock, HSF-1 binds well-conserved motifs, called Heat Shock Elements (HSEs), and drives expression of genes important for cellular protection during this stress. Remarkably, we found that substantial numbers of HSEs in multiple Caenorhabditis species reside within Helitrons, a type of DNA transposon. Consistent with Helitron-embedded HSEs being functional, upon heat shock they display increased HSF-1 and RNA polymerase II occupancy and up-regulation of nearby genes in C. elegans. Interestingly, we found that different genes appear to be incorporated into the HSR by species-specific Helitron insertions in C. elegans and C. briggsae and by strain-specific insertions among different wild isolates of C. elegans. Our studies uncover previously unidentified targets of HSF-1 and show that Helitron insertions are responsible for rewiring and diversifying the Caenorhabditis HSR.
24 citations
TL;DR: It is demonstrated that in Caenorhabditis elegans HS induces up- and downregulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene and repeat elements, providing new candidates that may contribute to organismal survival during this stress.
Abstract: Elevated temperatures activate a heat shock response (HSR) to protect cells from the pathological effects of protein mis-folding, cellular mis-organization, organelle dysfunction and altered membrane fluidity. This response includes activation of the conserved transcription factor heat shock factor 1 (HSF-1), which binds heat shock elements (HSEs) in the promoters of genes induced by heat shock (HS). The upregulation of protein-coding genes (PCGs), such as heat shock proteins and cytoskeletal regulators, is critical for cellular survival during elevated temperatures. While the transcriptional response of PCGs to HS has been comprehensively analyzed in a variety of organisms, the effect of this stress on the expression of non-coding RNAs (ncRNAs) has not been systematically examined. Here we show that in Caenorhabditis elegans HS induces up- and downregulation of specific ncRNAs from multiple classes, including miRNA, piRNA, lincRNA, pseudogene and repeat elements. Moreover, some ncRNA genes appear to be direct targets of the HSR, as they contain HSF-1 bound HSEs in their promoters and their expression is regulated by this factor during HS. These results demonstrate that multiple ncRNA genes respond to HS, some as direct HSF-1 targets, providing new candidates that may contribute to organismal survival during this stress.
23 citations
TL;DR: It is found that the reduced embryonic viability of mir-35-41(gk262) mutants is partially reversed by exogenous dsRNA via a mechanism that involves canonical RNAi, indicating cross-regulation between different small RNA pathways in C. elegans to regulate embryonic viability.
Abstract: RNA interference (RNAi) is a valuable technique to determine gene function. In Caenorhabditis elegans, RNAi can be achieved by feeding worms bacteria carrying a plasmid expressing double-stranded RNA (dsRNA) targeting a gene of interest. The most commonly used plasmid vector for this purpose is L4440. However, it has been noticed that sequences within L4440 may elicit unspecific effects. Here, we provide a comprehensive characterization of these effects and their mechanisms and describe new unexpected phenotypes uncovered by the administration of unspecific exogenous dsRNA. An example involves dsRNA produced by the multiple cloning site (MCS) of L4440, which shares complementary sequences with some widely used reporter vectors and induces partial transgene silencing via the canonical and antiviral RNAi pathway. Going beyond transgene silencing, we found that the reduced embryonic viability of mir-35-41(gk262) mutants is partially reversed by exogenous dsRNA via a mechanism that involves canonical RNAi. These results indicate cross-regulation between different small RNA pathways in C. elegans to regulate embryonic viability. Recognition of the possible unspecific effects elicited by RNAi vectors is important for rigorous interpretation of results from RNAi-based experiments.
18 citations
TL;DR: W worm biologists from the United States, Canada, and the United Kingdom gathered at the Colorado State University Todos Santos Center in Baja California Sur, Mexico, April 3–5, 2019 for the Todo Santos Small RNA Symposium, with the sort of laid-back vibe you might expect amongst the palm trees and ocean breeze of the Pacific coast of Mexico.
Abstract: Worm biologists from the United States, Canada, and the United Kingdom gathered at the Colorado State University Todos Santos Center in Baja California Sur, Mexico, April 3–5, 2019 for the Todos Sa...