scholarly journals Identification of PTBP1 responsible for caspase dependent YRNA cleavage

2018 ◽  
Author(s):  
Jun Ogata ◽  
Yuki Sugiura ◽  
Akinori Kanai ◽  
Masafumi Tanaka ◽  
Hirotaka Matsui ◽  
...  
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Caspase 3 ◽  
Biological Significance ◽  
Underlying Mechanism ◽  
Rna Degradation ◽  
Rna Cleavage ◽  
28S Rrna ◽  
U1 Snrna ◽  
Non Coding Rnas

ABSTRACTSome RNAs such as 28S rRNA, U1 snRNA, and Y RNAs are known to be cleaved during apoptosis. As the underlying mechanism is yet unclear, the functions and biological significance of RNA degradation in apoptosis remain elusive. We previously identified novel, functional small RNAs named AGO-taxis small RNA (ASR) that are specifically bound to AGO1. Here, we investigated ASR biogenesis, which appears to be non-canonical. Y RNAs, non-coding RNAs degraded during apoptosis, were identified as the precursors of several ASRs. Cell-free analysis combined with fractionation methods revealed that the apoptosis-specific biogenesis of ASRs or Y RNA degradation was induced by PTBP1—an endoribonuclease inhibitor of Y RNAs. PTBP1, a splicing factor, was truncated by caspase 3, which subsequently activated endoribonuclease to induce biogenesis of ASRs and Y RNA cleavage.

scholarly journals Small RNA modifications in Alzheimer’s disease

2020 ◽  
Author(s):  
Xudong Zhang ◽  
Fatima Trebak ◽  
Lucas AC Souza ◽  
Junchao Shi ◽  
Tong Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Prefrontal Cortex ◽  
Small Rna ◽  
Small Rnas ◽  
Post Mortem ◽  
Rna Modifications ◽  
Non Coding Rnas ◽  
And Control

AbstractBackgroundWhile significant advances have been made in uncovering the aetiology of Alzheimer’s disease and related dementias at the genetic level, molecular events at the epigenetic level remain largely undefined. Emerging evidence indicates that small non-coding RNAs (sncRNAs) and their associated RNA modifications are important regulators of complex physiological and pathological processes, including aging, stress responses, and epigenetic inheritance. However, whether small RNAs and their modifications are altered in dementia is not known.MethodsWe performed LC-MS/MS–based, high-throughput assays of small RNA modifications in post-mortem samples of the prefrontal lobe cortices of Alzheimer’s disease (AD) and control individuals. We noted that some of the AD patients has co-occurring vascular cognitive impairment-related pathology (VaD).FindingsWe report altered small RNA modifications in AD samples compared with normal controls. The 15–25-nucleotide (nt) RNA fraction of these samples was enriched for microRNAs, whereas the 30–40-nt RNA fraction was enriched for tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). Interestingly, most of these altered RNA modifications were detected both in the AD and AD with co-occurring vascular dementia subjects. In addition, sequencing of small RNA in the 30–40-nt fraction from AD cortices revealed reductions in rsRNA-5S, tsRNA-Tyr, and tsRNA-Arg.InterpretationThese data suggest that sncRNAs and their associated modifications are novel signals that may be linked to the pathogenesis and development of Alzheimer’s disease.FundingNIH grants (R01HL122770, R01HL091905, 1P20GM130459, R01HD092431, P50HD098593, GM103440), AHA grant (17IRG33370128), Sigmund Gestetner Foundation Fellowship to P Kehoe.Research in ContextEvidence before this studyAlzheimer’s disease (AD) and vascular dementia (VaD) are marked by cognitive impairment and neuropathologies caused by significant neuronal death. Associated gene mutations are rare in subjects with dementia, and the aetiology of these diseases is still not completely understood. Recent emerging evidence suggests that epigenetic changes are risk factors for the development of dementia. However, studies assessing small RNA modifications—one of the features of epigenetics—in dementia are lacking.Added value of this studyWe used high-throughput liquid chromatography-tandem mass spectrometry and small RNA sequencing to profile small RNA modifications and the composition of small RNAs in post-mortem samples of the prefrontal cortex of AD and control subjects. We detected and quantified 16 types of RNA modifications and identified distinct small non-coding RNAs and modification signatures in AD subjects compared with controls.Implications of all the available evidenceThis study identified novel types and compositions of small RNA modifications in the prefrontal cortex of AD patients compared with control subjects in post-mortem samples. The cellular locations of these RNA modifications and whether they are drivers or outcomes of AD are still not known. However, results from the present study may open new possibilities for dissecting the dementia pathology.

scholarly journals Polyploidy-associated paramutation in Arabidopsis is determined by small RNAs, temperature, and allele structure

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009444
Author(s):  
Heinrich Bente ◽  
Andrea M. Foerster ◽  
Nicole Lettner ◽  
Ortrun Mittelsten Scheid
Keyword(s):  
Arabidopsis Thaliana ◽  
Small Rna ◽  
Small Rnas ◽  
Underlying Mechanism ◽  
Mendelian Inheritance ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
F2 Population ◽  
Different Types ◽  
Allelic Interaction

Paramutation is a form of non-Mendelian inheritance in which the expression of a paramutable allele changes when it encounters a paramutagenic allele. This change in expression of the paramutable alleles is stably inherited even after segregation of both alleles. While the discovery of paramutation and studies of its underlying mechanism were made with alleles that change plant pigmentation, paramutation-like phenomena are known to modulate the expression of other traits and in other eukaryotes, and many cases have probably gone undetected. It is likely that epigenetic mechanisms are responsible for the phenomenon, as paramutation forms epialleles, genes with identical sequences but different expression states. This could account for the intergenerational inheritance of the paramutated allele, providing profound evidence that triggered epigenetic changes can be maintained over generations. Here, we use a case of paramutation that affects a transgenic selection reporter gene in tetraploid Arabidopsis thaliana. Our data suggest that different types of small RNA are derived from paramutable and paramutagenic epialleles. In addition, deletion of a repeat within the epiallele changes its paramutability. Further, the temperature during the growth of the epiallelic hybrids determines the degree and timing of the allelic interaction. The data further make it plausible why paramutation in this system becomes evident only in the segregating F2 population of tetraploid plants containing both epialleles. In summary, the results support a model for polyploidy-associated paramutation, with similarities as well as distinctions from other cases of paramutation.

scholarly journals Abolished miR158 activity leads to 21-nucleotide tertiary phasiRNA biogenesis that targets NHX2 in Arabidopsis thaliana

2021 ◽  
Author(s):  
Abhinandan Mani Tripathi ◽  
Rajneesh Singh ◽  
Akanksha Singh ◽  
Ashwani Kumar Verma ◽  
Parneeta Mishra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Rna ◽  
Small Rnas ◽  
Small Interfering Rnas ◽  
Primary Transcript ◽  
Over Expression ◽  
Additional Layer ◽  
Natural Variants ◽  
Non Coding Rnas

ABSTRACTSmall RNAs including microRNAs (miRNAs) are short 20-24-nucleotide non-coding RNAs. They are key regulators of gene expression in plants and other organisms. Some small RNAs, mostly 22-nucleotide long trigger biogenesis of secondary small interfering RNAs (siRNAs). Those siRNAs having distinctive phased configuration are known as phased siRNAs (phasiRNAs) and act either in cis or trans enhancing silencing cascade. Here, we report natural variants of MIR158 having deletions or insertions led to negligible or reduced expression of miR158. The deletion/insertion events affected processing of primary transcript of miR158 to precursor and to mature miR158. We show that miR158 targets a pseudo-pentatricopeptide gene and its abolished activity led to 21-nucleotide tertiary phasiRNA generation from its target. The biogenesis of these phasiRNAS is triggered by TAS2 derived two siRNAs. Accordingly, small RNA analyses of these natural variants, mutants and over-expression lines of MIR158 or its target exhibited enhanced or reduced phasiRNA biogenesis. Finally, we functionally validated the highest expressed tertiary phasiRNA that targets NHX2 thereby regulating transpiration and stomatal conductance. Overall, we deciphered a new module of small RNA network, miRNA-TAS-siRNA-pseudogene-tertiary phasiRNA-NHX2, suggesting an additional layer of gene regulation and larger role of pseudogene in plants.

scholarly journals Identification of Small RNAs During High Light Acclimation in Arabidopsis thaliana

2021 ◽  
Vol 12 ◽  
Author(s):  
Bhavika Tiwari ◽  
Kristin Habermann ◽  
M. Asif Arif ◽  
Oguz Top ◽  
Wolfgang Frank
Keyword(s):  
Small Rnas ◽  
Regulation Of Gene Expression ◽  
Biological Significance ◽  
Light Treatment ◽  
High Light ◽  
Light Acclimation ◽  
Light Conditions ◽  
Gene Pairs ◽  
High Light Treatment ◽  
Non Coding Rnas

The biological significance of non-coding RNAs (ncRNAs) has been firmly established to be important for the regulation of genes involved in stress acclimation. Light plays an important role for the growth of plants providing the energy for photosynthesis; however, excessive light conditions can also cause substantial defects. Small RNAs (sRNAs) are a class of non-coding RNAs that regulate transcript levels of protein-coding genes and mediate epigenetic silencing. Next generation sequencing facilitates the identification of small non-coding RNA classes such as miRNAs (microRNAs) and small-interfering RNAs (siRNAs), and long non-coding RNAs (lncRNAs), but changes in the ncRNA transcriptome in response to high light are poorly understood. We subjected Arabidopsis plants to high light conditions and performed a temporal in-depth study of the transcriptome data after 3 h, 6 h, and 2 days of high light treatment. We identified a large number of high light responsive miRNAs and sRNAs derived from NAT gene pairs, lncRNAs and TAS transcripts. We performed target predictions for differentially expressed miRNAs and correlated their expression levels through mRNA sequencing data. GO analysis of the targets revealed an overrepresentation of genes involved in transcriptional regulation. In A. thaliana, sRNA-mediated regulation of gene expression in response to high light treatment is mainly carried out by miRNAs and sRNAs derived from NAT gene pairs, and from lncRNAs. This study provides a deeper understanding of sRNA-dependent regulatory networks in high light acclimation.

scholarly journals Fidelity in RNA-based recognition of transposable elements

2018 ◽  
Vol 373 (1762) ◽  
pp. 20180168 ◽  
Author(s):  
Ilaria Ugolini ◽  
Mario Halic
Keyword(s):  
Transposable Elements ◽  
Small Rna ◽  
Small Rnas ◽  
Rna Degradation ◽  
Current Data ◽  
Theme Issue ◽  
Rna Pathways ◽  
Transposon Insertions

Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for degradation? This requires a system that is highly adaptable, and at the same time highly specific. Current data suggest that perturbation of transcription patterns by transposon insertions could be detected by the RNAi surveillance pathway. Multiple transposon insertions might generate sufficient amounts of primal small RNAs to initiate generation of secondary small RNAs and silencing. At the same time primal small RNAs need to be constantly degraded to reduce the level of noise small RNAs below the threshold required for initiation of silencing. Failure in RNA degradation results in loss of fidelity of small RNA pathways and silencing of ectopic targets. This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.

scholarly journals Emerging Functions for snoRNAs and snoRNA-Derived Fragments

2021 ◽  
Vol 22 (19) ◽  
pp. 10193
Author(s):  
Maliha Wajahat ◽  
Cameron Peter Bracken ◽  
Ayla Orang
Keyword(s):  
Small Rnas ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Biological Significance ◽  
Specific Interactions ◽  
Additional Source ◽  
Widespread Implementation ◽  
Non Coding Rna ◽  
Complex Picture ◽  
Non Coding Rnas

The widespread implementation of mass sequencing has revealed a diverse landscape of small RNAs derived from larger precursors. Whilst many of these are likely to be byproducts of degradation, there are nevertheless metabolically stable fragments derived from tRNAs, rRNAs, snoRNAs, and other non-coding RNA, with a number of examples of the production of such fragments being conserved across species. Coupled with specific interactions to RNA-binding proteins and a growing number of experimentally reported examples suggesting function, a case is emerging whereby the biological significance of small non-coding RNAs extends far beyond miRNAs and piRNAs. Related to this, a similarly complex picture is emerging of non-canonical roles for the non-coding precursors, such as for snoRNAs that are also implicated in such areas as the silencing of gene expression and the regulation of alternative splicing. This is in addition to a body of literature describing snoRNAs as an additional source of miRNA-like regulators. This review seeks to highlight emerging roles for such non-coding RNA, focusing specifically on “new” roles for snoRNAs and the small fragments derived from them.

scholarly journals Identifying small RNAs derived from maternal- and somatic-type rRNAs in zebrafish development

Genome ◽  
2018 ◽  
Vol 61 (5) ◽  
pp. 371-378 ◽  
Author(s):  
Mauro D. Locati ◽  
Johanna F.B. Pagano ◽  
Farah Abdullah ◽  
Wim A. Ensink ◽  
Marina van Olst ◽  
...  
Keyword(s):  
Small Rnas ◽  
Developmental Stages ◽  
28S Rrna ◽  
Stem Loop ◽  
Zebrafish Development ◽  
Common Precursor ◽  
Non Coding Rnas ◽  
Rrna Degradation ◽  
Generation Sequencing ◽  
Small Rnaseq

rRNAs are non-coding RNAs present in all prokaryotes and eukaryotes. In eukaryotes there are four rRNAs: 18S, 5.8S, 28S, originating from a common precursor (45S), and 5S. We have recently discovered the existence of two distinct developmental types of rRNA: a maternal-type, present in eggs and a somatic-type, expressed in adult tissues. Lately, next-generation sequencing has allowed the discovery of new small-RNAs deriving from longer non-coding RNAs, including small-RNAs from rRNAs (srRNAs). Here, we systemically investigated srRNAs of maternal- or somatic-type 18S, 5.8S, 28S, with small-RNAseq from many zebrafish developmental stages. We identified new srRNAs for each rRNA. For 5.8S, we found srRNA consisting of the 5′ or 3′ halves, with only the latter having different sequence for the maternal- and somatic-types. For 18S, we discovered 21 nt srRNA from the 5′ end of the 18S rRNA with a striking resemblance to microRNAs; as it is likely processed from a stem-loop precursor and present in human and mouse Argonaute-complexed small-RNA. For 28S, an abundant 80 nt srRNA from the 3′ end of the 28S rRNA was found. The expression levels during embryogenesis of these srRNA indicate they are not generated from rRNA degradation and might have a role in the zebrafish development.

scholarly journals The accumulation of chloroplast small RNAs in unicellular alga Chlamydomonas reinhardtii is affected by nitrogen deprivation

2019 ◽  
Author(s):  
Suhaimi Che-Ani ◽  
Ghows Azzam ◽  
Nazalan Najimudin
Keyword(s):  
Chlamydomonas Reinhardtii ◽  
Small Rna ◽  
Small Rnas ◽  
Metabolic Stress ◽  
Rrna Genes ◽  
Nitrogen Deprivation ◽  
Nitrogen Levels ◽  
Chloroplast Genomes ◽  
Non Coding Rnas ◽  
Genomic Locations

ABSTRACTSmall RNAs generated from the chloroplast genome may play a role in gene regulation. Given that chloroplast function is affected by nitrogen deprivation, there is yet an attempt to link chloroplast small RNAs to this stress condition. This study aims to determine the response of chloroplast small RNAs under nitrogen deprivation and their putative mode of action. A comparative transcriptomic approach was carried out to analyze the differential accumulation of chloroplast small RNAs from Chlamydomonas reinhardtii cells grown in nitrogen-deprived versus nitrogen-based medium. A total of 101 chloroplast small RNA candidates were successfully annotated. Growth in nitrogen-deprived medium revealed 17 significantly upregulated and 12 downregulated chloroplast small RNAs. These chloroplast small RNAs originated from different genomic locations such as untranslated, intergenic or antisense regions as well as the ends of tRNA and rRNA genes. The differentially accumulated csRNAs from 3’-untranslated regions were all upregulated. In contrast, the csRNAs from the ends of tRNA and rRNA genes were all downregulated during nitrogen deprivation. Fluctuations of the chloroplast small RNA levels indicated their importance in the chloroplasts during changes in nitrogen levels. The primary sequences of three selected chloroplast small RNA were found to be conserved in the chloroplast genomes of a few microalgae, again reflecting their functional importance. The findings from this study provided new insights into the involvement of non-coding RNAs in chloroplast during metabolic stress.

scholarly journals Contribution of Small RNA Pathway to Interactions of Rice with Pathogens and Insect Pests

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qin Feng ◽  
Yan Li ◽  
Zhi-Xue Zhao ◽  
Wen-Ming Wang
Keyword(s):  
Small Rna ◽  
Small Rnas ◽  
Recent Progress ◽  
Target Genes ◽  
Insect Pests ◽  
Circular Rnas ◽  
Small Interfering Rnas ◽  
Double Stranded Rna ◽  
Argonaute Proteins ◽  
Non Coding Rnas

AbstractSmall RNAs (sRNAs) are mainly classified into microRNAs (miRNAs) and small interfering RNAs (siRNAs) according to their origin. miRNAs originate from single-stranded RNA precursors, whereas siRNAs originate from double-stranded RNA precursors that are synthesized by RNA-dependent RNA polymerases. Both of single-stranded and double-stranded RNA precursors are processed into sRNAs by Dicer-like proteins. Then, the sRNAs are loaded into ARGONAUTE proteins, forming RNA-induced silencing complexes (RISCs). The RISCs repress the expression of target genes with sequences complementary to the sRNAs through the cleavage of transcripts, the inhibition of translation or DNA methylation. Here, we summarize the recent progress of sRNA pathway in the interactions of rice with various parasitic organisms, including fungi, viruses, bacteria, as well as insects. Besides, we also discuss the hormone signal in sRNA pathway, and the emerging roles of circular RNAs and long non-coding RNAs in rice immunity. Obviously, small RNA pathway may act as a part of rice innate immunity to coordinate with growth and development.

scholarly journals Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomonori Hara ◽  
Manabu Toyoshima ◽  
Yasuko Hisano ◽  
Shabeesh Balan ◽  
Yoshimi Iwayama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Caspase 3 ◽  
Intervention Strategy ◽  
Underlying Mechanism ◽  
Carbonyl Stress ◽  
Gene Encoding ◽  
Induced Pluripotent

AbstractCarbonyl stress, a specific form of oxidative stress, is reported to be involved in the pathophysiology of schizophrenia; however, little is known regarding the underlying mechanism. Here, we found that disruption of GLO1, the gene encoding a major catabolic enzyme scavenging the carbonyl group, increases vulnerability to external carbonyl stress, leading to abnormal phenotypes in human induced pluripotent stem cells (hiPSCs). The viability of GLO1 knockout (KO)-hiPSCs decreased and activity of caspase-3 was increased upon addition of methylglyoxal (MGO), a reactive carbonyl compound. In the GLO1 KO-hiPSC-derived neurons, MGO administration impaired neurite extension and cell migration. Further, accumulation of methylglyoxal-derived hydroimidazolone (MG-H1; a derivative of MGO)-modified proteins was detected in isolated mitochondria. Mitochondrial dysfunction, including diminished membrane potential and dampened respiratory function, was observed in the GLO1 KO-hiPSCs and derived neurons after addition of MGO and hence might be the mechanism underlying the effects of carbonyl stress. The susceptibility to MGO was partially rescued by the administration of pyridoxamine, a carbonyl scavenger. Our observations can be used for designing an intervention strategy for diseases, particularly those induced by enhanced carbonyl stress or oxidative stress.

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