Poly(A) tails: longer is not always better

Castellano, Luciana Andrea; Bazzini, Ariel

doi:10.1038/nsmb.3509

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…2). In general, in all the genotypes, the housekeeping genes had a slightly shorter poly(A) tail (with a mode of about 60 nt) than other (non-housekeeping) genes, which is consistent with recent reports of highly expressed genes tending to have a shorter poly(A) tail (10,11,32), and the actual values were similar to previous reports of the poly(A) lengths of Arabidopsis housekeeping genes (11). On the other hand, transcripts from TE regions tended to have the longest poly(A) tails in all the genotypes (Fig.…”

Section: Dna Methylation Was Positively Correlated With Poly(a) Tail Lengthsupporting

confidence: 91%

DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis

Chen

et al. 2021

Preprint

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Background: DNA methylation may regulate pre-mRNA transcriptional initiation and processing, thus affecting gene expression. Unlike animal cells, plants, especially Arabidopsis thaliana, have relatively low DNA methylation levels, limiting our ability to observe any correlation between DNA methylation and pre-mRNA processing using typical short-read sequencing. However, with newly developed long-read sequencing technologies, such as Oxford Nanopore Technology Direct RNA sequencing (ONT DRS), combined with whole-genome bisulfite sequencing, we were able to precisely analyze the relationship between DNA methylation and pre-mRNA transcriptional initiation and processing using DNA methylation-related mutants. Results: Using ONT DRS, we generated more than 2 million high-quality full-length long reads of native mRNA for each of the wild type Col-0 and mutants defective in DNA methylation, identifying a total of 117,474 isoforms. We found that low DNA methylation levels around splicing sites tended to prevent splicing events from occurring. The lengths of the poly(A) tail of mRNAs were positively correlated with DNA methylation. DNA methylation before transcription start sites or around transcription termination sites tended to result in gene-silencing or read-through events. Furthermore, using ONT DRS, we identified novel transcripts that we could not have otherwise, since transcripts with intron retention and fusion transcripts containing the uncut intergenic sequence tend not to be exported to the cytoplasm. Using the met1-3 mutant with activated constitutive heterochromatin regions, we confirmed the effects of DNA methylation on pre-mRNA processing. Conclusion: The combination of ONT DRS with whole-genome bisulfite sequencing was a powerful tool for studying the effects of DNA methylation on splicing site selection and pre-mRNA processing, and therefore regulation of gene expression.

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Section: Dna Methylation Was Positively Correlated With Poly(a) Tail Lengthsupporting

confidence: 91%

DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis

Chen

et al. 2021

Preprint

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“…Additionally, our poly(A) profiling revealed a distinct sexdependent distribution of poly(A) tail length. In general, our data align with previous observations that highly abundant housekeeping genes possess relatively short poly(A) tails (11,19). We confirmed this negative correlation between mRNA poly(A) tail length and expression level for C. elegans males and hermaphrodites.…”

Section: Discussionsupporting

confidence: 91%

TENT-5 regulates the expression of male-specific genes inCaenorhabditis elegans

Mackiewicz,

Liudkovska,

Dziembowski

2024

Preprint

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Polyadenylation is an important post-transcriptional process that governs mRNA stability and expression. Advancements in direct RNA sequencing in recent years have clarified many aspects of this intricate regulation, revealing the influence of various factors. Here, we used Nanopore Direct RNA Sequencing to investigate the association between genome-wide mRNA poly(A) tail profiles and sexual dimorphism inCaenorhabditis elegans. Our results demonstrate sex-dependent differences in both gene expression and poly(A) tail metabolism. Notably, we discovered that cytoplasmic poly(A) polymerase TENT-5 regulates multiple male-specific transcripts, predominantly encoding putative seminal fluid components with predicted extracellular localization. TENT-5 expression in male-specific tissues, such as seminal vesicle and vas deference, corroborates its functional significance. Intriguingly, despite extensive TENT-5-mediated polyadenylation of male-specific transcripts, males devoid of TENT-5 show no abnormalities in mating behavior, sperm morphology, or fertility. Our findings suggest that TENT-5 plays a role in regulating sex-related processes in males, although the physiological consequences remain to be fully elucidated.

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“…They observed the shorter A-tails (∼70 nt median tail length) were more associated with active/higher expressed genes compared to the longer A-tail (>95 nt median length). Thus, these studies indicated an optimal and a well-defined PA-tail length for efficient translation of mRNAs (96,97). In our study, the NQO1 longest isoform had ∼70 nt median length that ranged from 50–90 nts.…”

Section: Discussionmentioning

confidence: 80%

“…The earlier view that longer A-tails led to an increased translation efficiency (75,76), was supported by experiments using in vitro translation systems, or cellular reporter assays (61,80). However, with emerging studies, coupling of translation efficiency with PA-tail length has become a matter of debate (77–79,96,97). Two new studies have challenged the old view on the relationship between PA-tail length and translational efficiency using high throughput PA-tail sequencing in non-embryonic cells (77,78).…”

Section: Discussionmentioning

confidence: 99%

Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart

Sudheesh

Mohan

Francis

et al. 2019

Nucleic Acids Research

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Alternative polyadenylation (APA)-mediated 3′-untranslated region (UTR) shortening is known to increase protein expression due to the loss of miRNA regulatory sites. Yet, mRNAs with longer 3′-UTR also show enhanced protein expression. Here, we identify a mechanism by which longer transcripts generated by the distal-most APA site leads to increased protein expression compared to the shorter transcripts and the longer transcripts are positioned to regulate heart failure (HF). A Star-PAP target gene, NQO1 has three poly(A) sites (PA-sites) at the terminal exon on the pre-mRNA. Star-PAP selects the distal-most site that results in the expression of the longest isoform. We show that the NQO1 distal-specific mRNA isoform accounts for the majority of cellular NQO1 protein. Star-PAP control of the distal-specific isoform is stimulated by oxidative stress and the toxin dioxin. The longest NQO1 transcript has increased poly(A) tail (PA-tail) length that accounts for the difference in translation potentials of the three NQO1 isoforms. This mechanism is involved in the regulation of cardiac hypertrophy (CH), an antecedent condition to HF where NQO1 downregulation stems from the loss of the distal-specific transcript. The loss of NQO1 during hypertrophy was rescued by ectopic expression of the distal- but not the proximal- or middle-specific NQO1 mRNA isoforms in the presence of Star-PAP expression, and reverses molecular events of hypertrophy in cardiomyocytes.

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Poly(A) tails: longer is not always better

Cited by 6 publications

References 13 publications

DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis

DNA methylation affects pre-mRNA transcriptional initiation and processing in Arabidopsis

TENT-5 regulates the expression of male-specific genes inCaenorhabditis elegans

Star-PAP controlled alternative polyadenylation coupled poly(A) tail length regulates protein expression in hypertrophic heart

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