Down-regulation of 21A Alu RNA as a tool to boost proliferation maintaining the tissue regeneration potential of progenitor cells

Gigoni, Arianna; Costa, Delfina; Gaetani, Massimiliano; Tasso, Roberta; Villa, Federico; Florio, Tullio; Pagano, Aldo

doi:10.1080/15384101.2016.1181242

Cited by 3 publications

(1 citation statement)

References 37 publications

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“…Some human pre-miRNAs are synthesized by pol III [6], and obviously such lineage-specific pol III transcribed miRNA genes exist in other higher eukaryotes as well. A number of other ncRNAs transcribed by pol III from specific regions of human genome were described [7]; one of such RNAs is apparently involved in regulation of cell proliferation [8].…”

Section: Introductionmentioning

confidence: 99%

TATA-Like Boxes in RNA Polymerase III Promoters: Requirements for Nucleotide Sequences

Tatosyan

Stasenko

Koval

et al. 2020

IJMS

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tRNA and some other non-coding RNA genes are transcribed by RNA polymerase III (pol III), due to the presence of intragenic promoter, consisting of boxes A and B spaced by 30–40 bp. Such pol III promoters, called type 2, are also intrinsic to Short Interspersed Elements (SINEs). The contribution of 5′-flanking sequences to the transcription efficiency of genes containing type 2 promoters is still studied insufficiently. Here, we studied this issue, focusing on the genes of two small non-coding RNAs (4.5SH and 4.5SI), as well as B1 and B2 SINEs from the mouse genome. We found that the regions from position −31 to −24 may significantly influence the transcription of genes and SINEs. We studied the influence of nucleotide substitutions in these sites, representing TATA-like boxes, on transcription of 4.5SH and 4.5SI RNA genes. As a rule, the substitutions of A and T to G or C reduced the transcription level, although the replacement of C with A also lowered it. In 4.5SH gene, five distal nucleotides of −31/−24 box (TTCAAGTA) appeared to be the most important, while in the box −31/−24 of 4.5SI gene (CTACATGA), all nucleotides, except for the first one, contributed significantly to the transcription efficiency. Random sequences occurring at positions −31/−24 upstream of SINE copies integrated into genome, promoted their transcription with different efficacy. In the 5′-flanking sequences of 4.5SH and 4.5SI RNA genes, the recognition sites of CREB, C/EBP, and Sp1 factors were found, and their deletion decreased the transcription.

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Section: Introductionmentioning

confidence: 99%

TATA-Like Boxes in RNA Polymerase III Promoters: Requirements for Nucleotide Sequences

Tatosyan

Stasenko

Koval

et al. 2020

IJMS

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Alu RNA and their roles in human disease states

Gussakovsky

McKenna

2021

RNA Biology

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Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation

et al. 2017

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Recessive mutations in the ubiquitously expressed POLR3A gene cause one of the most frequent forms of childhood-onset hypomyelinating leukodystrophy (HLD): POLR3-HLD. POLR3A encodes the largest subunit of RNA Polymerase III (Pol III), which is responsible for the transcription of transfer RNAs (tRNAs) and a large array of other small non-coding RNAs. In order to study the central nervous system pathophysiology of the disease, we introduced the French Canadian founder Polr3a mutation c.2015G > A (p.G672E) in mice, generating homozygous knock-in (KI/KI) as well as compound heterozygous mice for one Polr3a KI and one null allele (KI/KO). Both KI/KI and KI/KO mice are viable and are able to reproduce. To establish if they manifest a motor phenotype, WT, KI/KI and KI/KO mice were submitted to a battery of behavioral tests over one year. The KI/KI and KI/KO mice have overall normal balance, muscle strength and general locomotion. Cerebral and cerebellar Luxol Fast Blue staining and measurement of levels of myelin proteins showed no significant differences between the three groups, suggesting that myelination is not overtly impaired in Polr3a KI/KI and KI/KO mice. Finally, expression levels of several Pol III transcripts in the brain showed no statistically significant differences. We conclude that the first transgenic mice with a leukodystrophy-causing Polr3a mutation do not recapitulate the childhood-onset HLD observed in the majority of human patients with POLR3A mutations, and provide essential information to guide selection of Polr3a mutations for developing future mouse models of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-017-0294-y) contains supplementary material, which is available to authorized users.

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Down-regulation of 21A Alu RNA as a tool to boost proliferation maintaining the tissue regeneration potential of progenitor cells

Cited by 3 publications

References 37 publications

TATA-Like Boxes in RNA Polymerase III Promoters: Requirements for Nucleotide Sequences

TATA-Like Boxes in RNA Polymerase III Promoters: Requirements for Nucleotide Sequences

Alu RNA and their roles in human disease states

Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation

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