Publications by authors named "Santiago Morell"

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons.

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The cell culture-based retrotransposition reporter assay has been (and is) an essential tool for the study of vertebrate Long INterspersed Elements (LINEs). Developed more than 20 years ago, this assay has been instrumental in characterizing the role of LINE-encoded proteins in retrotransposition, understanding how ribonucleoprotein particles are formed, how host factors regulate LINE mobilization, etc. Moreover, variations of the conventional assay have been developed to investigate the biology of other currently active human retrotransposons, such as Alu and SVA.

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Retrotransposons are a type of transposable element (TE) that have amplified to astonishing numbers in mammalian genomes, comprising more than a third of the human and mouse genomes. Long interspersed element class 1 (LINE-1 or L1) retrotransposons are abundant and currently active retroelements in the human and mouse genomes. Similarly, long terminal repeat (LTR)-containing retrotransposons are abundant in both genomes, although only active in mice.

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A major consequence of the world industrialized lifestyle is the increasing period of unnatural light in environments during the day and artificial lighting at night. This major change disrupts endogenous homeostasis with external circadian cues, which has been associated to higher risk of diseases affecting human health, mainly cancer among others. Circadian disruption promotes tumor development and accelerate its fast progression.

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Background: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.

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Long Interspersed Element class 1 retrotransposons (LINE-1 or L1) are abundant Transposable Elements in mammalian genomes and their mobility continues to impact the human genome. The development of engineered retrotransposition assays has been instrumental to understand how these elements are regulated and to identify domains involved in the process of retrotransposition. Additionally, the modification of a retrotransposition indicator cassette has allowed developing straightforward approaches to characterize the site of new L1 insertions in cultured cells.

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Long interspersed element 1 (LINE-1 or L1) retrotransposons have generated one-third of the human genome, and their ongoing mobility is a source of inter- and intraindividual genetic diversity. Although retrotransposition in metazoans has long been considered a germline phenomenon, recent experiments using cultured cells, animal models, and human tissues have revealed extensive L1 mobilization in rodent and human neurons, as well as mobile element activity in the Drosophila brain. In this review, we evaluate the available evidence for L1 retrotransposition in the brain and discuss mechanisms that may regulate neuronal retrotransposition in vivo.

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Half of the human genome is composed of repeated DNA, and some types are mobile within our genome (transposons and retrotransposons). Despite their abundance, only a small fraction of them are currently active in our genome (Long Interspersed Element-1 (LINE-1), Alu, and SVA elements). LINE-1 or L1 elements are a family of active non-LTR retrotransposons, the ongoing mobilization of which still impacts our genome.

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Article Synopsis
  • LINE-1s (L1s) are non-long-terminal-repeat retrotransposons found in the human genome and can mobilize both themselves and other elements like Alu, impacting human genetic diversity and diseases.
  • * The study discovered that several Alu subfamilies are active in undifferentiated human embryonic stem cells (hESCs), with the youngest Alu elements being most frequently expressed.
  • * Results suggest that L1s are mainly located within genes and their expression is epigenetically controlled, indicating a higher potential for genetic variation from L1 insertions during early human development than previously thought.
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Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution. L1s can retrotranspose in the germline, during early development and in select somatic cells; however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration.

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