mRNA turnover meets RNA interference.
By using two very different approaches, recent work by Gazzani et al. (2004) and Souret et al. (2004) reveal a fundamental link between mRNA degradation and RNA silencing pathways in Arabidopsis.
Arabidopsis↗
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Results for “microRNA expression”
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Time to grow up: the temporal role of smallRNAs in plants.
Over the past two years, several Arabidopsis genes that were initially identified as vegetative phase change mutants have been shown to have roles in smallRNA (sRNA) biogenesis. This has led to the identification of a new class of short interfering RNAs (siRNAs) called trans-acting siRNAs (ta-siRNAs).
Gene Expression Regulation, Developmental↗
RNA silencing and genome regulation.
Closely related RNA silencing phenomena such as posttranscriptional and transcriptional gene silencing (PTGS and TGS), quelling and RNA interference (RNAi) represent different forms of a conserved ancestral process. The biological relevance of these RNA-directed mechanisms of silencing in gene regulation, genome defence and chromosomal structure is rapidly being unravelled. Here, we review the recent developments in the field of RNA silencing in relation to other epigenetic phenomena and discuss the significance of this process and its targets in the regulation of modern eukaryotic genomes.
Animals↗
Micros for microbes: non-coding regulatory RNAs in bacteria.
Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent studies have led to the identification of numerous small regulatory RNAs in Escherichia coli and in other bacteria. As in eukaryotic cells, a major class of these small RNAs acts by base-pairing with target mRNAs, resulting in changes in the translation and stability of the mRNA. Roles for these non-coding pairing RNAs in bacteria have been demonstrated in several cases. Because these non-coding RNAs act post-transcriptionally, they impose a regulatory step that is independent of and epistatic to any transcriptional signals for their target mRNAs.
Bacterial Proteins↗
Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis.
The lin-4 and let-7 small temporal RNAs play a central role in controlling the timing of Caenorhabditis elegans cell fate decisions. let-7 has been conserved through evolution, and its expression correlates with adult development in bilateral animals, including Drosophila [Nature 408 (2000), 86]. The best match for lin-4 in Drosophila, miR-125, is also expressed during pupal and adult stages of Drosophila development [Curr. Biol. 12 (2002), 735]. Here, we ask whether the steroid hormone ecdysone induces let-7 or miR-125 expression at the onset of metamorphosis, attempting to link a known temporal regulator in Drosophila with the heterochronic pathway defined in C. elegans. We find that let-7 and miR-125 are coordinately expressed in late larvae and prepupae, in synchrony with the high titer ecdysone pulses that initiate metamorphosis. Unexpectedly, however, their expression is neither dependent on the EcR ecdysone receptor nor inducible by ecdysone in cultured larval organs. Although let-7 and miR-125 can be induced by ecdysone in Kc tissue culture cells, their expression is significantly delayed relative to that seen in the animal. let-7 and miR-125 are encoded adjacent to one another in the genome, and their induction correlates with the transient appearance of an approximately 500-nt RNA transcribed from this region, providing a mechanism to explain their precise coordinate regulation. We conclude that a common precursor RNA containing both let-7 and miR-125 is induced independently of ecdysone in Drosophila, raising the possibility of a temporal signal that is distinct from the well-characterized ecdysone-EcR pathway.
Animals↗
The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter.
MicroRNAs (miRNAs) are a large family of small regulatory RNAs that are poorly understood. The let-7 miRNA regulates the timing of the developmental switch from larval to adult cell fates during Caenorhabditis elegans development. Expression of let-7 RNA is temporally regulated, with robust expression in the fourth larval and adult stages. Here, we show that, like let-7 RNA, a transcriptional fusion of the let-7 promoter to gfp is temporally regulated, indicating that let-7 is transcriptionally controlled. Temporal upregulation of let-7 transcription requires an enhancer element, the temporal regulatory element (TRE), situated about 1200 base pairs upstream of the start of the mature let-7 RNA. The TRE is both necessary and sufficient for this temporal upregulation. A TRE binding factor (TREB) is able to bind to the TRE, and a 22-base pair inverted repeat within the TRE is necessary and sufficient for this binding. We also find that the nuclear hormone receptor DAF-12 and the RNA binding protein LIN-28 are both required for the correct timing of let-7 RNA and let-7::gfp expression. We speculate that these heterochronic genes regulate let-7 expression through its TRE.
Animals↗
Revealing micro-RNAs in plants.
Recent work has resulted in the identification of >100 endogenous non-coding small RNA molecules in plants. These micro-RNAs (miRNAs) have the capacity to regulate a range of predicted target mRNAs, many of which are transcription factors involved in the control of meristem identity. Mutants defective in either CARPEL FACTORY or Hen1 fail to accumulate miRNAs and have severe developmental defects. Thus, miRNAs are implicated as potentially key regulatory molecules in plant development.
Arabidopsis Proteins↗
Developmental biology: tiny brakes for a growing heart.
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Animals↗
Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors.
RNA silencing is an evolutionarily conserved system that functions as an antiviral mechanism in higher plants and insects. To counteract RNA silencing, viruses express silencing suppressors that interfere with both siRNA- and microRNA-guided silencing pathways. We used comparative in vitro and in vivo approaches to analyse the molecular mechanism of suppression by three well-studied silencing suppressors. We found that silencing suppressors p19, p21 and HC-Pro each inhibit the intermediate step of RNA silencing via binding to siRNAs, although the molecular features required for duplex siRNA binding differ among the three proteins. None of the suppressors affected the activity of preassembled RISC complexes. In contrast, each suppressor uniformly inhibited the siRNA-initiated RISC assembly pathway by preventing RNA silencing initiator complex formation.
Animals↗
Global mapping of c-Myc binding sites and target gene networks in human B cells.
The protooncogene MYC encodes the c-Myc transcription factor that regulates cell growth, cell proliferation, cell cycle, and apoptosis. Although deregulation of MYC contributes to tumorigenesis, it is still unclear what direct Myc-induced transcriptomes promote cell transformation. Here we provide a snapshot of genome-wide, unbiased characterization of direct Myc binding targets in a model of human B lymphoid tumor using ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET). Myc potentially occupies > 4,000 genomic loci with the majority near proximal promoter regions associated frequently with CpG islands. Using gene expression profiles with ChIP-PET, we identified 668 direct Myc-regulated gene targets, including 48 transcription factors, indicating that Myc is a central transcriptional hub in growth and proliferation control. This first global genomic view of Myc binding sites yields insights of transcriptional circuitries and cis regulatory modules involving Myc and provides a substantial framework for our understanding of mechanisms of Myc-induced tumorigenesis.
B-Lymphocytes↗
The bantam gene regulates Drosophila growth.
We report here the consequences of mutations of a novel locus, named bantam, whose product is involved in the regulation of growth in Drosophila. bantam mutant animals are smaller than wild type, due to a reduction in cell number but not cell size, and do not have significant disruptions in patterning. Conversely, overexpression of the bantam product using the EP element EP(3)3622 causes overgrowth of wing and eye tissue. Overexpression in clones of cells results in an increased rate of cell proliferation and a matched increase in cellular growth rate, such that the resulting tissue is composed of more cells of a size comparable to wild type. These effects are strikingly similar to those associated with alterations in the activity of the cyclinD-cdk4 complex. However, epistasis and genetic interaction analyses indicate that bantam and cyclinD-cdk4 operate independently. Thus, the bantam locus represents a novel regulator of tissue growth.
Animals↗
Post-transcriptional small RNA pathways in plants: mechanisms and regulations.
Small RNAs are riboregulators that have critical roles in most eukaryotes. They repress gene expression by acting either on DNA to guide sequence elimination and chromatin remodeling, or on RNA to guide cleavage and translation repression. This review focuses on the various types of post-transcriptional small RNA-directed pathways in plants, describing their roles and their regulations.
DNA Methylation↗
The exoribonuclease XRN4 is a component of the ethylene response pathway in Arabidopsis.
EXORIBONUCLEASE4 (XRN4), the Arabidopsis thaliana homolog of yeast XRN1, is involved in the degradation of several unstable mRNAs. Although a role for XRN4 in RNA silencing of certain transgenes has been reported, xrn4 mutant plants were found to lack any apparent visible phenotype. Here, we show that XRN4 is allelic to the unidentified components of the ethylene response pathway ETHYLENE-INSENSITIVE5/ACC-INSENSITIVE1 (EIN5/AIN1) and EIN7. xrn4 mutant seedlings are ethylene-insensitive as a consequence of the upregulation of EIN3 BINDING F-BOX PROTEIN1 (EBF1) and EBF2 mRNA levels, which encode related F-box proteins involved in the turnover of EIN3 protein, a crucial transcriptional regulator of the ethylene response pathway. Epistasis analysis placed XRN4/EIN5/AIN1 downstream of CTR1 and upstream of EBF1/2. XRN4 does not appear to regulate ethylene signaling via an RNA-INDUCED SILENCING COMPLEX-based RNA silencing mechanism but acts by independent means. The identification of XRN4 as an integral new component in ethylene signaling adds RNA degradation as another posttranscriptional process that modulates the perception of this plant hormone.
Alleles↗
Cloning and characterization of micro-RNAs from moss.
Micro-RNAs (miRNAs) are one class of endogenous tiny RNAs that play important regulatory roles in plant development and responses to external stimuli. To date, miRNAs have been cloned from higher plants such as Arabidopsis, rice and pumpkin, and there is limited information on their identity in lower plants including Bryophytes. Bryophytes are among the oldest groups of land plants among the earth's flora, and are important for our understanding of the transition to life on land. To identify miRNAs that might have played a role early in land plant evolution, we constructed a library of small RNAs from the juvenile gametophyte (protonema) of the moss Physcomitrella patens. Sequence analysis revealed five higher plant miRNA homologues, including three members of the miR319 family, previously shown to be involved in the regulation of leaf morphogenesis, and miR156, which has been suggested to regulate several members of the SQUAMOSA PROMOTER BINDING-LIKE (SPL) family in Arabidopsis. We have cloned PpSBP3, a moss SPL homologue that contains an miR156 complementary site, and demonstrated that its mRNA is cleaved within that site suggesting that it is an miR156 target in moss. Six additional candidate moss miRNAs were identified and shown to be expressed in the gametophyte, some of which were developmentally regulated or upregulated by auxin. Our observations suggest that miRNAs play important regulatory roles in mosses.
Base Sequence↗
Novel micro-RNAs and intermediates of micro-RNA biogenesis from moss.
Micro-RNAs (miRNAs) are one class of small non-coding RNAs that have important regulatory roles in higher plants. Much less is known about their prevalence and function in lower land plants. Previously we cloned 100 non-structural small RNAs from the moss Physcomitrella patens but could annotate only 11 as miRNAs. To identify additional moss miRNAs among cloned small RNAs we have analyzed their genomic sequences for a characteristic miRNA precursor-like structure. This analysis revealed 19 new moss miRNAs that are predicted to be encoded by 22 putative foldbacks. Northern blot analysis confirmed the expression of 14 new miRNA representatives. Half of these were gametophore specific, the rest were detected at low levels in the protonema. We predicted 12 genes as targets of nine new miRNAs. Three of these show homology to transcription factors and the others appear to play roles in diverse physiological processes including light and cytokine signaling, which have not to date been shown to be regulated by a miRNA in flowering plants. Four target genes, which show homology to ATN1-like protein kinase, NAC transcription factors and a cytokinin receptor, have been validated by miRNA-mediated mRNA cleavage. In addition, our analysis revealed that seven small RNAs represent miRNA* and three represent intermediates of pre-miRNA processing, providing evidence for specific DICER-like cleavage steps during miRNA biogenesis in moss. Our findings suggest that miRNAs are common in mosses and set the stage for the elucidation of their varied biological functions.
Base Sequence↗
Breakthrough of the year.
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Biomedical Research↗