Genome-wide analysis of polymerase III–transcribed <i>Alu</i> elements suggests cell-type–specific enhancer function

Zhang, Xiao‐Ou; Gingeras, T; Weng, Zhiping

doi:10.1101/gr.249789.119

Cited by 71 publications

(79 citation statements)

References 54 publications

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“…Early studies have shown that RNAPIII is responsible for the transcription of small noncoding RNAs, such as transfer RNAs (tRNAs), 5S ribosomal RNA (rRNA), U6 small nuclear RNA, and 7SL RNA (RN7SL1 RNA) in eukaryotes (Paule and White, 2000;Geiduschek and Kassavetis, 2001;Dieci et al, 2007). These small noncoding RNAs play widespread roles in basic biological activities, including protein synthesis (tRNAs), ribosome biogenesis (5S rRNA; Ciganda and Williams, 2011), mRNA splicing (U6 small nuclear RNA), membrane targeting of newly translated proteins (7SL RNA; Dieci et al, 2002), and selective mRNA export (SINE RNAs; Ponicsan et al, 2010;Karijolich et al, 2017) and they also act as cell-type-specific enhancers (Alu elements; Hardeland and Hurt, 2006;Zhang et al, 2019). These findings suggest that RNA-PIII is required for growth, development, and reproduction (Goodfellow and White, 2007;Filer et al, 2017).…”

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confidence: 99%

Loss of Function of an RNA Polymerase III Subunit Leads to Impaired Maize Kernel Development

et al. 2020

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Kernel size is an important factor determining grain yield. Although a number of genes affecting kernel development in maize (Zea mays) have been identified by analyzing kernel mutants, most of the corresponding mutants cannot be used in maize breeding programs due to low germination or incomplete seed development. Here, we characterized small kernel7, a recessive small-kernel mutant with a mutation in the gene encoding the second-largest subunit of RNA polymerase III (RNAPΙΙΙ; NRPC2). A frame shift in ZmNRPC2 leads to a premature stop codon, resulting in significantly reduced levels of transfer RNAs and 5S ribosomal RNA, which are transcribed by RNAPΙΙΙ. Loss-of-function nrpc2 mutants created by CRISPR/CAS9 showed significantly reduced kernel size due to altered endosperm cell size and number. ZmNRPC2 affects RNAPIII activity and the expression of genes involved in cell proliferation and endoreduplication to control kernel development via physically interacting with RNAPIII subunits RPC53 and AC40, transcription factor class C1 and Floury3. Notably, unlike the semidominant negative mutant floury3, which has defects in starchy endosperm, small kernel7 only affects kernel size but not the composition of kernel storage proteins. Our findings provide novel insights into the molecular network underlying maize kernel size, which could facilitate the genetic improvement of maize in the future.

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confidence: 99%

Loss of Function of an RNA Polymerase III Subunit Leads to Impaired Maize Kernel Development

et al. 2020

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“…In yeast RNA pol II transcriptional activity was demonstrated in the rDNA non-coding regions [52], and the pol II derived transcripts were shown to regulate nucleolar dynamics in higher eukaryotes [53]. In addition, the ribosomal intergenic spacer contains multiple Alu-repeats, evolutionarily originated from 7SL RNA genes [54], and may be potentially transcribed by RNA pol III [55]. We further plan to determine both the enzyme involved in the transcription of the non-coding RNAs detected in the current study and regulation of their expression.…”

Section: Discussionmentioning

confidence: 99%

Mapping and Quantification of Non-Coding RNA Originating from the rDNA in Human Glioma Cells

Sadova

Kupriyanova

Pavlova

2020

Cancers

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Ribosomal DNA is one of the most conserved parts of the genome, especially in its rRNA coding regions, but some puzzling pieces of its noncoding repetitive sequences harbor secrets of cell growth and development machinery. Disruptions in the neat mechanisms of rDNA orchestrating the cell functioning result in malignant conversion. In cancer cells, the organization of rRNA coding genes and their transcription somehow differ from that of normal cells, but little is known about the particular mechanism for this switch. In this study, we demonstrate that the region ~2 kb upstream of the rDNA promoter is transcriptionally active in one type of the most malignant human brain tumors, and we compare its expression rate to that of healthy human tissues and cell cultures. Sense and antisense non-coding RNA transcripts were detected and mapped, but their secondary structure and functions remain to be elucidated. We propose that the transcripts may relate to a new class of so-called promoter-associated RNAs (pRNAs), or have some other regulatory functions. We also hope that the expression of these non-coding RNAs can be used as a marker in glioma diagnostics and prognosis.

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“…Recent studies have revealed a link between Alu elements and the control of gene expression (Hanke et al, 1995;Mallona et al, 2016;Chen et al, 2018). Many of these findings came from extensive computational analyses of genome-wide epigenomic and transcriptomic data (Goerner-Potvin and Bourque, 2018;Zhang et al, 2019); however, the direct functional testing of Alu sequences and their contribution repeat to gene regulatory networks have remained poorly explored.…”

Section: Discussionmentioning

confidence: 99%

An Intronic Alu Element Attenuates the Transcription of a Long Non-coding RNA in Human Cell Lines

et al. 2020

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Alu elements are primate-specific repeats and represent the most abundant type of transposable elements (TE) in the human genome. Genome-wide analysis of the enrichment of histone post-translational modifications suggests that human Alu sequences could function as transcriptional enhancers; however, no functional experiments have evaluated the role of Alu sequences in the control of transcription in situ. The present study analyses the regulatory activity of a human Alu sequence from the AluSx family located in the second intron of the long intergenic non-coding RNA Linc00441, found in divergent orientation to the RB1 gene. We observed that the Alu sequence acts as an enhancer element based on reporter gene assays while CRISPR-Cas9 deletions of the Alu sequence in K562 cells resulted in a marked transcriptional upregulation of Linc00441 and a decrease in proliferation. Our results suggest that an intragenic Alu sequence with enhancer activity can act as a transcriptional attenuator of its host lincRNA.

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Genome-wide analysis of polymerase III–transcribed Alu elements suggests cell-type–specific enhancer function

Cited by 71 publications

References 54 publications

Loss of Function of an RNA Polymerase III Subunit Leads to Impaired Maize Kernel Development

Loss of Function of an RNA Polymerase III Subunit Leads to Impaired Maize Kernel Development

Mapping and Quantification of Non-Coding RNA Originating from the rDNA in Human Glioma Cells

An Intronic Alu Element Attenuates the Transcription of a Long Non-coding RNA in Human Cell Lines

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