MicroRNAs, a class of small noncoding RNAs, play key roles in diverse biological and pathological processes. ER stress, resulting from the accumulation of unfolded or misfolded proteins in the ER lumen, is triggered by various physiological events and pathological insults. Here, using RNA deep sequencing analysis, we found that the expression of some microRNAs was altered in HeLa and HEK293 cells under ER stress. Protein and RNA levels of DGCR8, Drosha, Exportin-5, Dicer, and Ago2 showed no significant alteration in ER-stressed cells, which suggested that the change in microRNA expression might not be caused by the microRNA biogenesis pathway but by other, unknown factors. Real-time PCR assays confirmed that hsa-miR-423-5p was up-regulated, whereas hsa-miR-221-3p and hsa-miR-452-5p were down-regulated, in both HeLa and HEK293 cells under ER stress. Luciferase activity and Western blot assays verified that CDKN1A was a direct target of hsa-miR-423-5p and that CDKN1B was a direct target of hsa-miR-221-3p and hsamiR-452-5p. We speculated that by regulating their targets, microRNAs might function cooperatively as regulators in the adaptive response to ER stress.
A major portion of the mammalian genome is transcribed to produce large numbers of noncoding RNAs(ncRNAs).During the past decade,the discovery of small RNAs,including the microRNAs(miRNA) and small interfering RNAs(siRNA),has led to important advances in biology.The breadth of the ncRNA field of study has substantially expanded and many recent results have revealed a range of functions that can be attributed to the miRNAs and other ncRNAs.For example,H19 RNA,HOTAIR RNA,transcribed ultraconserved regions(T-UCRs),natural antisense RNA,transfer RNA and mitochondrial noncoding RNA have been suggested to play important roles in cancers and other diseases as well as in diverse cellular processes.In this review,we focus on the current status of several classes of ncRNAs associated with cancer with the emphasis on those that are not microRNAs.
Animals interact with their environments all the time,and must react to all kinds of factors present in the environments.Environmental RNA interference refers to the phenomenon that exogenous RNA molecules can enter cells of certain animal species and interfere with gene expression of these animals.These exogenous RNAs may be molecules in animal food,or may be present in the living environment from other sources.Molecular pathways for the cell entry of environmental RNAs and further for their functionality in gene interference have started to be revealed in the animal model Caenorhabditis elegans.Here we highlight some known examples of environmental RNA interference(RNAi)in animals and introduce the molecular mechanisms underneath.
MENG LingFengCHEN LiangLI ZhaoYongWU ZhengXingSHAN Ge
Most eukaryotes employ a variety of mechanisms to defend the integrity of their genome by recognizing and silencing parasitic mobile nucleic acids.However,recent studies have shown that genomic DNA undergoes extensive rearrangements,including DNA elimination,fragmentation,and unscrambling,during the sexual reproduction of ciliated protozoa.Non-coding RNAs have been identified to program and regulate genome rearrangement events.In Paramecium and Tetrahymena,scan RNAs(scnRNAs)are produced from micronuclei and transported to vegetative macronuclei,in which scnRNA elicits the elimination of cognate genomic DNA.In contrast,Piwi-interacting RNAs(piRNAs)in Oxytricha enable the retention of genomic DNA that exhibits sequence complementarity in macronuclei.An RNA interference(RNAi)-like mechanism has been found to direct these genomic rearrangements.Furthermore,in Oxytricha,maternal RNA templates can guide the unscrambling process of genomic DNA.The non-coding RNA-directed genome rearrangements may have profound evolutionary implications,for example,eliciting the multigenerational inheritance of acquired adaptive traits.