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International Journal of Molecular... Oct 2021Mitochondria have their own double-stranded DNA genomes and systems to regulate transcription, mRNA processing, and translation. These systems differ from those... (Review)
Review
Mitochondria have their own double-stranded DNA genomes and systems to regulate transcription, mRNA processing, and translation. These systems differ from those operating in the host cell, and among eukaryotes. In recent decades, studies have revealed several plant-specific features of mitochondrial gene regulation. The polyadenylation status of mRNA is critical for its stability and translation in mitochondria. In this short review, I focus on recent advances in understanding the mechanisms regulating mRNA polyadenylation in plant mitochondria, including the role of poly(A)-specific ribonuclease-like proteins (PARNs). Accumulating evidence suggests that plant mitochondria have unique regulatory systems for mRNA poly(A) status and that PARNs play pivotal roles in these systems.
Topics: Embryophyta; Exoribonucleases; Gene Expression Regulation, Plant; Mitochondria; Poly A; Polyadenylation; RNA Stability; RNA, Messenger; RNA, Mitochondrial
PubMed: 34639116
DOI: 10.3390/ijms221910776 -
Scientific Reports Sep 2022In this work, we looked at how to make fluorescence hybrid poly(amidoamine) dendrimer (PAMAM) dendrimers using calcozine red 6G and coumarin end groups. After synthesis...
In this work, we looked at how to make fluorescence hybrid poly(amidoamine) dendrimer (PAMAM) dendrimers using calcozine red 6G and coumarin end groups. After synthesis of ethylenediamine (EDA)-cored 4th generation PAMAM dendrimer (G4.0), surface functional groups is reacted with calcozine red 6G (Rh6G) and 7-methacryloyloxy-4-methylcoumarin. Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (H NMR), and X-ray diffraction are used to characterize the structure of synthesized fluorescent hybrid dendrimers. Optical properties are demonstrated using a fluorescence spectrophotometer, and UV-Vis-NIR reflectance spectra. According to UV-Vis-NIR reflectance spectra, hybrid dendrimers were transparent in the NIR range. Moreover, quantum yield (Φs) of hybrid dendrimers was calculated in dimethylformamide (DMF), ethanol, dimethyl sulfoxide (DMSO), and distilled water (HO). Dendrimers in which Rh6G was utilized to modification showed the maximum quantum yield in ethanol due to great interaction of structure with ethanol and the arrangement of ring-opened amide shape of calcozine red 6G.
Topics: Dendrimers; Ethanol; Fluorescence; Poly A; Polyamines
PubMed: 36071149
DOI: 10.1038/s41598-022-19712-5 -
Nature Aug 2017A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal...
A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3' terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility. In comparison to somatic cells, the oocyte transcriptome has a shorter poly(A) tail and a higher relative proportion of terminal oligo-uridylation. Deletion of TUT4 and TUT7 leads to the accumulation of a cohort of transcripts with a high frequency of very short poly(A) tails, and a loss of 3' oligo-uridylation. By contrast, deficiency of TUT4 and TUT7 does not alter gene expression in a variety of somatic cells. In summary, we show that poly(A) tail length and 3' terminal uridylation have essential and specific functions in shaping a functional maternal transcriptome.
Topics: Animals; Cell Line; DNA-Binding Proteins; Female; Infertility, Female; Male; Maternal Inheritance; Mice; Mice, Knockout; Mothers; Nucleotidyltransferases; Oocytes; Organ Specificity; Poly A; RNA Stability; RNA, Messenger; Transcriptome; Uridine Monophosphate
PubMed: 28792939
DOI: 10.1038/nature23318 -
Molecular Cell Dec 2015L1 retrotransposons express proteins (ORF1p and ORF2p) that preferentially mobilize their encoding RNA in cis, but they also can mobilize Alu RNA and, more rarely,...
L1 retrotransposons express proteins (ORF1p and ORF2p) that preferentially mobilize their encoding RNA in cis, but they also can mobilize Alu RNA and, more rarely, cellular mRNAs in trans. Although these RNAs differ in sequence, each ends in a 3' polyadenosine (poly(A)) tract. Here, we replace the L1 polyadenylation signal with sequences derived from a non-polyadenylated long non-coding RNA (MALAT1), which can form a stabilizing triple helix at the 3' end of an RNA. L1/MALAT RNAs accumulate in cells, lack poly(A) tails, and are translated; however, they cannot retrotranspose in cis. Remarkably, the addition of a 16 or 40 base poly(A) tract downstream of the L1/MALAT triple helix restores retrotransposition in cis. The presence of a poly(A) tract also allows ORF2p to bind and mobilize RNAs in trans. Thus, a 3' poly(A) tract is critical for the retrotransposition of sequences that comprise approximately one billion base pairs of human DNA.
Topics: Endonucleases; HeLa Cells; Humans; Long Interspersed Nucleotide Elements; Poly A; RNA, Long Noncoding; RNA, Messenger; RNA-Directed DNA Polymerase
PubMed: 26585388
DOI: 10.1016/j.molcel.2015.10.012 -
PloS One 2023The sterilization of medical devices is paramount to achieve an acceptable level of sterility assurance and to prevent hospital-acquired infections. However, some...
The sterilization of medical devices is paramount to achieve an acceptable level of sterility assurance and to prevent hospital-acquired infections. However, some medical devices cannot be sterilized by usual processes such as autoclave (AC) and gamma-ray irradiation (GI). A new non-thermal plasma (NTP) process using sealed bag that preserves the sterile state of the devices could be used as an alternative sterilization method. The aim of the study was to assess the cytocompatibility of titanium and poly(etheretherketone) (PEEK) surfaces after O2-NTP sterilization compared to GI and AC. MG-63 osteoblast-like cells were seeded on titanium (TA6V) and PEEK disks sterilized by AC, GI and O2-NTP. The cells' viability and proliferation, determined by WST-1 and DNA quantification respectively, were enhanced whatever the material types from 3 to 10 days. When seeded on titanium, MG-63 cells showed a higher viability and proliferation after GI and O2-NTP treatment compared to AC treatment. When cultured on PEEK, MG-63 cells showed a higher viability after O2-NTP treatment. No difference of proliferation was observed whatever the sterilization processes. The cell colonization of the materials' surface was confirmed by scanning electron microscopy. Lactate dehydrogenase (LDH) assay revealed no cytotoxicity. Thus, O2-NTP led to similar cell responses to AC and GI and could be a cost-effective alternative process to the usual sterilization methods for fragile medical devices.
Topics: Humans; Titanium; Poly A; Sterilization; Benzophenones; Infertility; Plasma Gases
PubMed: 37647324
DOI: 10.1371/journal.pone.0290820 -
Nature Structural & Molecular Biology Dec 2017Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not...
Poly(A) tails are important elements in mRNA translation and stability, although recent genome-wide studies have concluded that poly(A) tail length is generally not associated with translational efficiency in nonembryonic cells. To investigate whether poly(A) tail size might be coupled to gene expression in an intact organism, we used an adapted TAIL-seq protocol to measure poly(A) tails in Caenorhabditis elegans. Surprisingly, we found that well-expressed transcripts contain relatively short, well-defined tails. This attribute appears to be dependent on translational efficiency, as transcripts enriched for optimal codons and ribosome association had the shortest tail sizes, whereas noncoding RNAs retained long tails. Across eukaryotes, short tails were a feature of abundant and well-translated mRNAs. This seems to contradict the dogma that deadenylation induces translational inhibition and mRNA decay and suggests that well-expressed mRNAs accumulate with pruned tails that accommodate a minimal number of poly(A)-binding proteins, which may be ideal for protective and translational functions.
Topics: Animals; Caenorhabditis elegans; Gene Expression; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Peptide Chain Elongation, Translational; Poly A; RNA, Messenger; RNA, Untranslated
PubMed: 29106412
DOI: 10.1038/nsmb.3499 -
Biochimica Et Biophysica Acta Jan 2016Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have... (Review)
Review
Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have a 5' cap and a poly(A) tail, yet some of the most abundant long noncoding RNAs are processed in unexpected ways and lack these canonical structures. Here, I highlight the mechanisms by which several of these well-characterized noncoding RNAs are generated, stabilized, and function. The MALAT1 and MEN β (NEAT1_2) long noncoding RNAs each accumulate to high levels in the nucleus, where they play critical roles in cancer progression and the formation of nuclear paraspeckles, respectively. Nevertheless, MALAT1 and MEN β are not polyadenylated as the tRNA biogenesis machinery generates their mature 3' ends. In place of a poly(A) tail, these transcripts are stabilized by highly conserved triple helical structures. Sno-lncRNAs likewise lack poly(A) tails and instead have snoRNA structures at their 5' and 3' ends. Recent work has additionally identified a number of abundant circular RNAs generated by the pre-mRNA splicing machinery that are resistant to degradation by exonucleases. As these various transcripts use non-canonical strategies to ensure their stability, it is becoming increasingly clear that long noncoding RNAs may often be regulated by unique post-transcriptional control mechanisms. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.
Topics: Cell Nucleus; Gene Expression Regulation; Humans; Poly A; RNA Precursors; RNA Processing, Post-Transcriptional; RNA Splicing; RNA Stability; RNA, Long Noncoding; RNA, Small Nucleolar
PubMed: 26073320
DOI: 10.1016/j.bbagrm.2015.06.003 -
RNA Biology Feb 2017Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth... (Review)
Review
Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can reduce canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions. To date, a number of alternative translation mechanisms have been reported, which include non-canonical, cap dependent translation and cap independent translation such as IRES mediated translation. Here, we discuss one of the alternative modes of translation mediated by a specialized microRNA complex, FXR1a-microRNP that promotes non-canonical, cap dependent translation in quiescent conditions, where canonical translation is reduced due to low mTOR activity.
Topics: Animals; Argonaute Proteins; Eukaryotic Initiation Factor-4G; Exoribonucleases; Fragile X Mental Retardation Protein; Gene Expression Regulation; Humans; MicroRNAs; Poly A; Protein Binding; Protein Biosynthesis; RNA Cap-Binding Proteins; RNA Caps; RNA, Messenger; TOR Serine-Threonine Kinases
PubMed: 27911187
DOI: 10.1080/15476286.2016.1265197 -
NAR Genomics and Bioinformatics Sep 2023Alternative polyadenylation is a main driver of transcriptome diversity in mammals, generating transcript isoforms with different 3' ends via cleavage and...
Alternative polyadenylation is a main driver of transcriptome diversity in mammals, generating transcript isoforms with different 3' ends via cleavage and polyadenylation at distinct polyadenylation (poly(A)) sites. The regulation of cell type-specific poly(A) site choice is not completely resolved, and requires quantitative poly(A) site usage data across cell types. 3' end-based single-cell RNA-seq can now be broadly used to obtain such data, enabling the identification and quantification of poly(A) sites with direct experimental support. We propose SCINPAS, a computational method to identify poly(A) sites from scRNA-seq datasets. SCINPAS modifies the read deduplication step to favor the selection of distal reads and extract those with non-templated poly(A) tails. This approach improves the resolution of poly(A) site recovery relative to standard software. SCINPAS identifies poly(A) sites in genic and non-genic regions, providing complementary information relative to other tools. The workflow is modular, and the key read deduplication step is general, enabling the use of SCINPAS in other typical analyses of single cell gene expression. Taken together, we show that SCINPAS is able to identify experimentally-supported, known and novel poly(A) sites from 3' end-based single-cell RNA sequencing data.
PubMed: 37705828
DOI: 10.1093/nargab/lqad079 -
PLoS Computational Biology Apr 2020The mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription...
The mammalian circadian clock is deeply rooted in rhythmic regulation of gene expression. Rhythmic transcriptional control mediated by the circadian transcription factors is thought to be the main driver of mammalian circadian gene expression. However, mounting evidence has demonstrated the importance of rhythmic post-transcriptional controls, and it remains unclear how the transcriptional and post-transcriptional mechanisms collectively control rhythmic gene expression. In mouse liver, hundreds of genes were found to exhibit rhythmicity in poly(A) tail length, and the poly(A) rhythms are strongly correlated with the protein expression rhythms. To understand the role of rhythmic poly(A) regulation in circadian gene expression, we constructed a parsimonious model that depicts rhythmic control imposed upon basic mRNA expression and poly(A) regulation processes, including transcription, deadenylation, polyadenylation, and degradation. The model results reveal the rhythmicity in deadenylation as the strongest contributor to the rhythmicity in poly(A) tail length and the rhythmicity in the abundance of the mRNA subpopulation with long poly(A) tails (a rough proxy for mRNA translatability). In line with this finding, the model further shows that the experimentally observed distinct peak phases in the expression of deadenylases, regardless of other rhythmic controls, can robustly cluster the rhythmic mRNAs by their peak phases in poly(A) tail length and abundance of the long-tailed subpopulation. This provides a potential mechanism to synchronize the phases of target gene expression regulated by the same deadenylases. Our findings highlight the critical role of rhythmic deadenylation in regulating poly(A) rhythms and circadian gene expression.
Topics: Adenine; Animals; Circadian Clocks; Computational Biology; Computer Simulation; Gene Expression Regulation; Liver; Mice; Models, Genetic; Poly A; Polyadenylation; RNA, Messenger
PubMed: 32339166
DOI: 10.1371/journal.pcbi.1007842