Factors influencing degradation kinetics of mRNAs and half-lives of microRNAs, circRNAs, lncRNAs in blood in vitro using quantitative PCR

Wang, Chong; Liu, Hui

doi:10.1038/s41598-022-11339-w

Cited by 27 publications

(23 citation statements)

References 49 publications

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“…For half-life calculation, the antigen concentration (U-value) was calculated from the ratio-value according to the regression equation, where C 0 was the initial antigen concentration, and C 10 was the antigen concentration after 10 days ( t = 10). The half-life (T 1/2 ) of the antigen was calculated using the following equation (Wang and Liu 2022 ): …”

Section: Methodsmentioning

confidence: 99%

Determining half-life of SARS-CoV-2 antigen in respiratory secretion

Guang

Liu

2023

Environ Sci Pollut Res

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted from person to person through respiratory droplets and aerosols. It is also possible for the virus to be transmitted indirectly through environmental contamination. The likelihood of environmental transmission depends on several factors, including the survival time of the virus in respiratory secretions. However, the stability of SARS-CoV-2 in respiratory secretions has not been investigated. In this study, we compared the half-life of the SARS-CoV-2 antigen in respiratory secretion under different conditions. We applied respiratory secretion (5 µL) to glass slides, air-dried the slides for 1 h, and kept them at 24 °C or 4 °C for 10 days. Respiratory secretions were also placed in test tubes (sealed to preserve moisture) and in normal saline for 10 days. The concentration of SARS-CoV-2 antigen in all samples was simultaneously measured using colloidal gold immunochromatography, and the half-life of the antigen was calculated. The half-life of the antigen in the wet (sealed tube) and saline samples at room temperature was 5.0 and 2.92 days, respectively. The half-life of the antigen in the air-dried sample at room temperature and at 4 °C was 2.93 and 11.4 days, respectively. The half-life was longer in respiratory secretions than that in normal saline. The half-life was also longer in respiratory secretions, at a lower temperature, and under wet conditions. Therefore, environmental transmission can also play a significant role in the spread of the virus. Robust prevention and control strategies could be developed based on the half-life of the antigen in respiratory secretions.

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Section: Methodsmentioning

confidence: 99%

Determining half-life of SARS-CoV-2 antigen in respiratory secretion

Guang

Liu

2023

Environ Sci Pollut Res

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“…We found that adenosine to inosine (A>I) RNA editing strongly promotes translation of circRNAs [12,13], suggesting that inosines could provide a ribosomal entry site. CircRNAs are more stable than linear mRNAs, with a half-life of 2-4 days [14,15], which compares to an average half-life of 4 hrs for mRNAs [16]. Due to intramolecular base pairing, circRNAs form rod-like structures with extended double strand RNA sequences [17], and are thus more prone to undergo modifications by ADAR enzymes (adenine deaminase acting on RNA) that recognize double stranded RNA structures and convert adenosines into inosines [18].…”

Section: Introduction 11 Circtau Rnasmentioning

confidence: 99%

Influence of FTDP-17 mutants on circular Tau RNAs

Margvelani,

Welden,

Maquera

et al. 2023

Preprint

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At least 53 mutations in the microtubule associated protein tau gene (MAPT) have been identified that cause frontotemporal dementia. 47 of these mutations are localized between exons 7 and 13. They could thus affect the formation of circular RNAs (circRNAs) from the MAPT gene that occur through backsplicing from exon 12 to either exon 10 or exon 7. We analyzed representative mutants and found that five FTDP-17 mutations increase the formation of 12->7 circRNA and three different mutations increase the amount of 12->10 circRNA. CircRNAs are translated after undergoing adenosine to inosine RNA editing, catalyzed by ADAR enzymes. We found that the interferon induced ADAR1-p150 isoform has the strongest effect on circTau RNA translation. ADAR1-p150 activity had a stronger effect on circTau RNA expression and strongly decreased 12->7 circRNA, but unexpectedly increased 12->10 circRNA. In both cases, ADAR-activity strongly promoted translation of circTau RNAs. Unexpectedly, we found that the 12->7 circTau protein interacts with eukaryotic initiation factor 4B (eIF4B), which is reduced by four FTDP-17 mutations located in the second microtubule domain. These are the first studies of the effect of human mutations on circular RNA formation and translation. They show that point mutations influence circRNA expression levels, likely through changes in the secondary pre-mRNA structures. The effect of the mutations is surpassed by editing of the circular RNAs, leading to their translation. Thus, circular RNAs and their editing status should be considered when analyzing FTDP-17 mutations.

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“…As circRNAs lack ends, they are generally resistant to exoribonucleases with approximately 2.5-fold longer half-lives than their linear counterparts (37, 38). CircRNAs are also more stable in the extracellular space, a feature which has led to much interest in their potential use as a diagnostic biomarker (39). Circularity, however, does not prevent susceptibility of circRNAs to endoribonucleases (endoRNases) such as RNase L and RNase P (40, 41).…”

Section: Introductionmentioning

confidence: 99%

Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection

Dremel,

Tagawa,

Koparde

et al. 2023

Preprint

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A first line of defense during infection is expression of interferon (IFN)-stimulated gene products which suppress viral lytic infection. To combat this, herpesviruses express endoribonucleases to deplete host RNAs. Here we demonstrate that IFN-induced circular RNAs (circRNAs) can escape viral-mediated degradation. We performed comparative circRNA expression profiling for representative alpha- (Herpes simplex virus-1, HSV-1), beta- (human cytomegalovirus, HCMV), and gamma-herpesviruses (Kaposi sarcoma herpesvirus, KSHV; murine gamma-herpesvirus 68, MHV68). Strikingly, we found that circRNAs are, as a population, resistant to host shutoff. This observation was confirmed by ectopic expression assays of human and murine herpesvirus endoribonucleases. During primary lytic infection, ten circRNAs were commonly regulated across all subfamilies of human herpesviruses, suggesting a common mechanism of regulation. We tested one such mechanism, namely how interferon-stimulation influences circRNA expression. 67 circRNAs were upregulated by either IFN-beta or -gamma treatment, with half of these also upregulated during lytic infection. Using gain and loss of function studies we found an interferon-stimulated circRNA, circRELL1, inhibited lytic HSV-1 infection. We have previously reported circRELL1 inhibits lytic KSHV infection, suggesting a pan-herpesvirus antiviral activity. We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape.

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Factors influencing degradation kinetics of mRNAs and half-lives of microRNAs, circRNAs, lncRNAs in blood in vitro using quantitative PCR

Cited by 27 publications

References 49 publications

Determining half-life of SARS-CoV-2 antigen in respiratory secretion

Determining half-life of SARS-CoV-2 antigen in respiratory secretion

Influence of FTDP-17 mutants on circular Tau RNAs

Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection

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