RNA Turnover in Bacteria, Archaea and Organelles

Abstract The cytochrome b gene in Saccharomyces cerevisiae, COB, is encoded by the mitochondrial genome. Nuclear-encoded Cbp1 protein is required specifically for COB mRNA stabilization. Cbp1 interacts with a CCG element in a 64-nucleotide sequence in the 5′-untranslated region of COB mRNA. Mutation of any nucleotide in the CCG causes the same phenotype as cbp1 mutations, i.e., destabilization of both COB precursor and mature message. In this study, eleven nuclear suppressors of single-nucleotide mutations in CCG were isolated and characterized. One dominant suppressor is in CBP1, while the other 10 semidominant suppressors define five distinct linkage groups. One group of four mutations is in PET127, which is required for 5′ end processing of several mitochondrial mRNAs. Another mutation is linked to DSS1, which is a subunit of mitochondrial 3′ → 5′ exoribonuclease. A mutation linked to the SOC1 gene, previously defined by recessive mutations that suppress cbp1 ts alleles and stabilize many mitochondrial mRNAs, was also isolated. We hypothesize that the products of the two uncharacterized genes also affect mitochondrial RNA turnover.

Download Full-text

c-myc RNA degradation in growing and differentiating cells: possible alternate pathways

Molecular and Cellular Biology ◽

10.1128/mcb.9.1.288-295.1989 ◽

1989 ◽

Vol 9 (1) ◽

pp. 288-295

Author(s):

S G Swartwout ◽

A J Kinniburgh

Keyword(s):

Actinomycin D ◽

Rna Degradation ◽

Transcriptional Elongation ◽

Rna Turnover ◽

Rapid Degradation ◽

Polyadenylated Rna ◽

Myc Gene ◽

Fail Safe ◽

Kinetics Of ◽

In Cells

Transcripts of the proto-oncogene c-myc are composed of a rapidly degraded polyadenylated RNA species and an apparently much more stable, nonadenylated RNA species. In this report, the extended kinetics of c-myc RNA turnover have been examined in rapidly growing cells and in cells induced to differentiate. When transcription was blocked with actinomycin D in rapidly growing cells, poly(A)+ c-myc was rapidly degraded (t1/2 = 12 min). c-myc RNA lacking poly(A) initially remained at or near control levels; however, after 80 to 90 min it was degraded with kinetics similar to those of poly(A)+ c-myc RNA. These bizarre kinetics are due to the deadenylation of poly(A)+ c-myc RNA to form poly(A)- c-myc, thereby initially maintaining the poly(A)- c-myc RNA pool when transcription is blocked. In contrast to growing cells, cells induced to differentiate degraded both poly(A)+ and poly(A)- c-myc RNA rapidly. The rapid disappearance of both RNA species in differentiating cells suggests that a large proportion of the poly(A)+ c-myc RNA was directly degraded without first being converted to poly(A)- c-myc RNA. Others have shown that transcriptional elongation of the c-myc gene is rapidly blocked in differentiating cells. We therefore hypothesize that in differentiating cells a direct, rapid degradation of poly(A)+ c-myc RNA may act as a backup or fail-safe system to ensure that c-myc protein is not synthesized. This tandem system of c-myc turnoff may also make cells more refractory to mutations which activate constitutive c-myc expression.

Download Full-text

Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells

Blood ◽

10.1182/blood.v79.5.1319.bloodjournal7951319 ◽

1992 ◽

Vol 79 (5) ◽

pp. 1319-1326 ◽

Cited By ~ 1

Author(s):

MR Baer ◽

P Augustinos ◽

AJ Kinniburgh

Keyword(s):

Acute Myeloid Leukemia ◽

Posttranscriptional Regulation ◽

Myeloid Leukemia ◽

Actinomycin D ◽

The Other ◽

Rna Turnover ◽

Gm Csf ◽

Acute Myeloid Leukemia Cells ◽

Acute Myeloid ◽

In Cells

Dysregulated expression of the c-myc and c-myb protooncogenes has been implicated in the pathogenesis of acute myeloid leukemia (AML). To elucidate mechanisms of c-myc dysregulation in AML cells, we studied c- myc RNA turnover in peripheral blood blasts from eight patients using actinomycin D transcription blockade. Rapid c-myc RNA turnover was seen in cells from six patients, with half-lives of approximately 30 minutes, similar to those reported in normal myeloid cells, in HL-60 cells, and in other cell lines. c-myc RNA turnover was prolonged in cells of the other two patients, with half-lives of greater than 75 minutes. c-fos RNA turnover was rapid in blasts from all eight patients, with half-lives of approximately 15 minutes. Stabilization of GM-CSF transcripts was not observed. In contrast, c-myb RNA half-lives were greater than 75 minutes in cells of the two patients with prolonged c-myc RNA turnover, as compared to 30 minutes in cells of the other six patients. Enhanced stability of both c-myc and c-myb RNA species suggests that a defect exists in a trans-acting factor that destabilizes both of these normally labile RNAs. Incomplete correlation between c-myc RNA levels and half-lives indicates regulation of c-myc expression at the level of transcription or nuclear transport in addition to posttranscriptional regulation.

Download Full-text

NUDT2 initiates viral RNA degradation by removal of 5′-phosphates

Nature Communications ◽

10.1038/s41467-021-27239-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Beatrice T. Laudenbach ◽

Karsten Krey ◽

Quirin Emslander ◽

Line Lykke Andersen ◽

Alexander Reim ◽

...

Keyword(s):

Rna Degradation ◽

Degradation Pathway ◽

Immune Defense ◽

Viral Rna ◽

Rna Turnover ◽

Nudix Hydrolase ◽

Cellular Mechanisms ◽

Independent Manner ◽

Viral Rnas ◽

Bacterial Rna

AbstractWhile viral replication processes are largely understood, comparably little is known on cellular mechanisms degrading viral RNA. Some viral RNAs bear a 5′-triphosphate (PPP-) group that impairs degradation by the canonical 5′-3′ degradation pathway. Here we show that the Nudix hydrolase 2 (NUDT2) trims viral PPP-RNA into monophosphorylated (P)-RNA, which serves as a substrate for the 5′-3′ exonuclease XRN1. NUDT2 removes 5′-phosphates from PPP-RNA in an RNA sequence- and overhang-independent manner and its ablation in cells increases growth of PPP-RNA viruses, suggesting an involvement in antiviral immunity. NUDT2 is highly homologous to bacterial RNA pyrophosphatase H (RppH), a protein involved in the metabolism of bacterial mRNA, which is 5′-tri- or diphosphorylated. Our results show a conserved function between bacterial RppH and mammalian NUDT2, indicating that the function may have adapted from a protein responsible for RNA turnover in bacteria into a protein involved in the immune defense in mammals.

Download Full-text