BioEssays, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 26, 2024
LINE-1 (L1) elements represent the largest family of transposable in mammalian genomes, making up approximately 21% and 17% mouse human genome, respectively. While most these are no longer intact, a significant number with potentially functional promoters, primarily from evolutionarily youngest families both species, scattered throughout genome. These L1 autonomously expressed encode RNAs, which however not necessarily translated into proteins, nor do complete their retrotransposition cycle to generate new insertions. In this issue, hypothesis article by Mangoni et al. refers as "L1 paradox," where an increase expression levels does lead proportional protein levels, or observable mobilization.[1] Several observations may help explain part paradox. First, accumulation mutations has rendered many noncoding, which, result, contribute pool L1-encoded proteins. Second, posttranscriptional control mechanisms host restrict export translation thereby contributing accumulation. Third, RNAs tend be short lived, retained nucleus, bound chromatin, often found close proximity site transcription. This retention occur through interactions chromatin nuclear factors that have affinity for RNAs.[2-4] Based on observations, authors propose additional explanation resolve paradox, focusing cooperation between L1s host. They hypothesize that, specific contexts, cells can leverage using them long noncoding (lncRNAs) beneficial regulatory potential promote cellular growth proliferation, while exploit states enhance chance mobilize during mitosis. A substantial body evidence supports role acting highlights mitogenic potential. During early embryogenesis, increased essential developmental progression accessibility.[5] embryonic stem (ESCs), they sustain proliferation self-renewal appear regulate transcriptional programs, crucial transitions across different stages, cells.[3, 4] brain development, high were shown cell neural progenitor (NPCs), preventing activation pathways neuronal differentiation.[2, 6] At mechanistic level, association subunits polycomb repressive complex 2 (PRC2), prevents repression genes support NPC proliferation.[2] Importantly, effects independent retrotransposition, remain unaffected reverse-transcriptase inhibitors. Interestingly, seem conserved cells, well despite differences genomic localization individual poor evolutionary conservation subfamily sequences two species. further reinforces RNAs. hypothesis, emphasize interaction proteins is critical potential, sequence modules secondary structures. then modulate activity, binding act molecular scaffolds assemble complexes, similar fashion lncRNAs. This, turn, could influence regulation entire programs delay differentiation.[1] would stages when cell-fate decisions made, maintenance cells. It remains seen whether other adult also exhibit higher levels. model, accommodate certain level whose detrimental diluted population thanks rapid divisions.[1] key remaining question at what point becomes pathological Is there threshold non-coding if exceeded, triggers toxicity its own, harm due retrotransposition? such cases, compromised genome integrity conditions, including neurological disorders cancer. However, it still unclear how misregulation directly causes disease. past research largely focused advocates exploring excessive alone disrupt drive disease development. comments paper Damiano al., https://doi.org/10.1002/bies.202400125 work was supported Portuguese FCT-Fundação para Ciência e Tecnologia, I.P., CEECIND/02085/2018 2022.02195.PTDC, International Rett Syndrome Foundation (grant #3909). The author declares conflicts interest.
Язык: Английский
