ribosomal rna processing
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Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 177-182
Author(s):  
Munenori Kitagawa ◽  
Peipei Wu ◽  
Rachappa Balkunde ◽  
Patrick Cunniff ◽  
David Jackson

mRNA migration through plasmodesmata In plants, certain transcription factors are produced in one cell but transported, sometimes as messenger RNA (mRNA), through plasmodesmata, channels between neighboring plant cells, where they act. This system helps to manage stem cell development. Kitagawa et al . now identify part of the machinery that manages this cell-to-cell transport. Transport of the mRNA encoding the KNOTTED1 homeobox transcription factor depends on Ribosomal RNA-Processing Protein 44 (AtRRP44A), which is a subunit of the RNA exosome. —PJH


2021 ◽  
Vol 36 (11) ◽  
pp. 2464-2467
Author(s):  
Geena Skariah ◽  
Roger Lee Albin

2021 ◽  
Author(s):  
Chan Ding ◽  
Yingjie Sun ◽  
Wei Wu ◽  
Yang Qu ◽  
Shengqing Yu ◽  
...  

DEAD (Glu-Asp-Ala-Glu)-box RNA helicases have been proven to contribute to antiviral innate immunity. DDX21 RNA helicase was identified as a nuclear protein involved in ribosomal RNA processing and RNA unwinding. DDX21 was also proved to be the scaffold protein in the complex of DDX1-DDX21-DHX36 which senses double strand RNA and initiates downstream innate immunity. Here, we identified that DDX21 undergoes caspase-dependent cleavage after virus infection and treatment with RNA/DNA ligands, especially for RNA virus and ligands. Caspase-3/6 cleave DDX21 at D126 and promotes its translocation from the nucleus to the cytoplasm in response to virus infection. The cytoplasmic cleaved DDX21 negatively regulates the IFN-β signaling pathway by suppressing the formation of DDX1-DDX21-DHX36 complex. Thus, our data identify DDX21 as a regulator of immune balance and most importantly uncover a potential role of DDX21 cleavage in the innate immunity response towards virus.


2021 ◽  
Author(s):  
Pavel Kudrin ◽  
David Meierhofer ◽  
Cathrine Broberg Vågbø ◽  
Ulf Andersson Vang Ørom

AbstractA large number of RNA modifications are known to affect processing and function of rRNA, tRNA and mRNA 1. The N4-acetylcytidine (ac4C) is the only known RNA acetylation event and is known to occur on rRNA, tRNA and mRNA 2,3. RNA modification by acetylation affects a number of biological processes, including translation and RNA stability 2. For a few RNA methyl modifications, a reversible nature has been demonstrated where specific writer proteins deposit the modification and eraser proteins can remove them by oxidative demethylation 4–6. The functionality of RNA modifications is often mediated by interaction with reader proteins that bind dependent on the presence of specific modifications 1. The NAT10 acetyltransferase has been firmly identified as the main writer of acetylation of cytidine ribonucleotides, but so far neither readers nor erasers of ac4C have been identified 2,3. Here we show, that ac4C is bound by the nucleolar protein NOP58 and deacetylated by SIRT7, for the first time demonstrating reversal by another mechanism than oxidative demethylation. NOP58 and SIRT7 are involved in snoRNA function and pre-ribosomal RNA processing 7–10, and using a NAT10 deficient cell line we can show that the reduction in ac4C levels affects both snoRNA sub-nuclear localization and pre-rRNA processing. SIRT7 can deacetylate RNA in vitro and endogenous levels of ac4C on snoRNA increase in a SIRT7 deficient cell line, supporting its endogenous function as an RNA deacetylase. In summary, we identify the first eraser and reader proteins of the RNA modification ac4C, respectively, and suggest an involvement of RNA acetylation in snoRNA function and pre-rRNA processing.


PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009215
Author(s):  
Joshua J. Black ◽  
Richa Sardana ◽  
Ezzeddine W. Elmir ◽  
Arlen W. Johnson

The first metastable assembly intermediate of the eukaryotic ribosomal small subunit (SSU) is the SSU Processome, a large complex of RNA and protein factors that is thought to represent an early checkpoint in the assembly pathway. Transition of the SSU Processome towards continued maturation requires the removal of the U3 snoRNA and biogenesis factors as well as ribosomal RNA processing. While the factors that drive these events are largely known, how they do so is not. The methyltransferase Bud23 has a role during this transition, but its function, beyond the nonessential methylation of ribosomal RNA, is not characterized. Here, we have carried out a comprehensive genetic screen to understand Bud23 function. We identified 67 unique extragenic bud23Δ-suppressing mutations that mapped to genes encoding the SSU Processome factors DHR1, IMP4, UTP2 (NOP14), BMS1 and the SSU protein RPS28A. These factors form a physical interaction network that links the binding site of Bud23 to the U3 snoRNA and many of the amino acid substitutions weaken protein-protein and protein-RNA interactions. Importantly, this network links Bud23 to the essential GTPase Bms1, which acts late in the disassembly pathway, and the RNA helicase Dhr1, which catalyzes U3 snoRNA removal. Moreover, particles isolated from cells lacking Bud23 accumulated late SSU Processome factors and ribosomal RNA processing defects. We propose a model in which Bud23 dissociates factors surrounding its binding site to promote SSU Processome progression.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Farooq ◽  
Louise Lindbæk ◽  
Nicolai Krogh ◽  
Canan Doganli ◽  
Cecilie Keller ◽  
...  

AbstractPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-40
Author(s):  
Timothy M Chlon ◽  
Emily Stepanchick ◽  
Daniel Starczynowski ◽  
Kathleen Hueneman

Germline mutations in the DEAD-box RNA helicase gene DDX41 cause inherited susceptibility to Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). These patients have normal hematopoietic indices into adulthood and present with MDS at a median age of 61 years, slightly younger than the general MDS patient population (71 years). Germline DDX41 mutations are always heterozygous and are typically frame-shift mutations, causing loss of function of the protein. More than half of these patients acquire a second-hit mutation in the healthy DDX41 allele in their disease clones. Greater than 80% of the second-hit mutations cause the amino acid substitution R525H, which results in loss of helicase activity. Multiple functions have been ascribed to DDX41, such as functioning as an innate immune sensor, a component of the RNA spliceosome, and a regulator of ribosomal RNA processing; however, its role in the pathogenesis of MDS remains poorly understood. To mimic the DDX41 mutations in human patients, we generated conditional mouse models of the most common DDX41 mutations, D140fs and R525H. We found that DDX41 is essential for the viability and function of hematopoietic stem and progenitor cells (HSPCs) and that R525H mutations render DDX41 inactive. We have also reported that mice with biallelic DDX41 mutations develop progressive anemia, dysplasia, and marrow failure. HSPCs lacking wild-type Ddx41 have dysfunctional ribosomes and reduced protein translation, leading to cycle arrest and apoptosis. As a mechanistic basis for the ribosome defect in Ddx41-deficient HSPCs, we found that loss of Ddx41 causes a profound increase in unprocessed snoRNA transcripts, which likely interrupts their cellular function. Importantly, we did not observe a change in host gene transcript abundance, and thus it is unlikely that the defects observed in Ddx41-deficient cells are caused by loss of the protein products of the host genes. SnoRNAs regulate ribosomal RNA (rRNA) by catalyzing post-transcriptional modifications, including methylation and pseudouridylation. Since the majority of the snoRNAs that were found to be unprocessed in Ddx41-deficient HSPCs were from the SNORA family, which is involved in pseudouridylation, we quantified the abundance of pseudouridine at specific sites in ribosomal RNA and found it to be reduced in Ddx41-deficient HSPCs. Utilizing global high-throughput sequencing approaches to analyze DDX41 binding to RNAs, we found that DDX41 preferentially binds to snoRNAs relative to all other types of RNA in the cells. Thus, DDX41 binds to snoRNAs and is essential for snoRNA processing, snoRNA-mediated rRNA pseudouridylation, and protein translation in HSPCs. These findings provide critical mechanistic insight into the protein translation defect that we and others have observed in DDX41-deficient cells and uncover the basis of ineffective hematopoiesis in MDS patients with DDX41 mutations. Disclosures Starczynowski: Tolero Therapeutics: Research Funding; Kurome Therapeutics: Consultancy, Current equity holder in private company, Research Funding; Captor Therapeutics: Consultancy.


Science ◽  
2020 ◽  
Vol 370 (6513) ◽  
pp. 227-231
Author(s):  
Haijun Wu ◽  
Xiaoya Qu ◽  
Zhicheng Dong ◽  
Linjie Luo ◽  
Chen Shao ◽  
...  

Stem cells in plants constantly supply daughter cells to form new organs and are expected to safeguard the integrity of the cells from biological invasion. Here, we show how stem cells of the Arabidopsis shoot apical meristem and their nascent daughter cells suppress infection by cucumber mosaic virus (CMV). The stem cell regulator WUSCHEL responds to CMV infection and represses virus accumulation in the meristem central and peripheral zones. WUSCHEL inhibits viral protein synthesis by repressing the expression of plant S-adenosyl-l-methionine–dependent methyltransferases, which are involved in ribosomal RNA processing and ribosome stability. Our results reveal a conserved strategy in plants to protect stem cells against viral intrusion and provide a molecular basis for WUSCHEL-mediated broad-spectrum innate antiviral immunity in plants.


2020 ◽  
Vol 432 (20) ◽  
pp. 5614-5631 ◽  
Author(s):  
Phoolwanti Rani ◽  
Shashwath Malli Kalladi ◽  
Harsh Bansia ◽  
Sandhya Rao ◽  
Rajiv Kumar Jha ◽  
...  

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