ABSTRACT
PIWI-interacting small RNAs (piRNAs) protect the germline genome and are essential for fertility. piRNAs originate from transposable element (TE) RNAs, long non-coding RNAs, or 3´ untranslated regions (3´UTRs) of protein-coding messenger genes, with the last being the least characterized of the three piRNA classes. Here, we demonstrate that the precursors of 3´UTR piRNAs are full-length mRNAs and that post-termination 80S ribosomes guide piRNA production on 3´UTRs in mice and chickens. At the pachytene stage, when other co-translational RNA surveillance pathways are sequestered, piRNA biogenesis degrades mRNAs right after pioneer rounds of translation and fine-tunes protein production from mRNAs. Although 3´UTR piRNA precursor mRNAs code for distinct proteins in mice and chickens, they all harbor embedded TEs and produce piRNAs that cleave TEs. Altogether, we discover a function of the piRNA pathway in fine-tuning protein production and reveal a conserved piRNA biogenesis mechanism that recognizes translating RNAs in amniotes.
Subject(s)
3' Untranslated Regions , Fertility/genetics , Protein Biosynthesis , RNA, Small Interfering/genetics , Ribosomes/genetics , Spermatogenesis/genetics , Animals , Base Sequence , Chickens , DNA Transposable Elements , Gene Expression Regulation , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Pachytene Stage , RNA, Small Interfering/metabolism , Ribosomes/metabolism , Testis/cytology , Testis/growth & development , Testis/metabolismABSTRACT
BACKGROUND: Asthma prevalence continues to increase in low and middle-income countries, presenting challenges in assessing asthma control in resource-poor settings. Previous studies suggest that exhaled carbon monoxide (eCO) is higher with asthma severity and lower with treatment. We hypothesized that eCO levels may be elevated in children with asthma, particularly in children with partially controlled or uncontrolled asthma in a low-resource setting in Lima, Peru. METHODS: We compared average eCO levels between 248 children with asthma and 221 healthy controls as well as the odds of asthma by eCO quartiles (0-1, 2, 3, and ≥4â¯ppm) using multivariable linear and logistic regression. eCO quartiles were also used to compare the odds of partially controlled or uncontrolled asthma (score ≤19 on the Asthma Control Test) in a multivariable logistic regression model. FINDINGS: Average adjusted eCO level was 0.56â¯ppm (95% CI 0.07-1.05) higher in children with asthma. The adjusted odds of asthma were 1.22 (95% CI 0.75-1.97), 1.46 (0.81-2.63), and 1.76 (0.96-3.23) in the second, third, and fourth eCO quartiles compared to the first eCO quartile, respectively. Among children with asthma, the adjusted odds of partially controlled or uncontrolled asthma in those in the second, third, and fourth eCO quartiles, compared to the first, were 1.61 (95% CI 0.74-3.48), 3.66 (95% CI 1.51-8.87), and 2.50 (95% CI 1.06-5.90), respectively. INTERPRETATION: eCO may serve as an inexpensive biomarker for asthma control, particularly in low-resource settings.
