SlideServe
Télécharger Obtenir Pro
Menu
Accueil Pro
Préférences
ApparenceLight Aide et commentaires
© SlideServe · v2026

Understanding Long Interspersed Nucleotide Elements (LINEs) and Their Role in the Human Genome

amber-lopez avatar
amber-lopez
12 diapositives · 294 Views · Nov 18, 2014

Long Interspersed Nucleotide Elements (LINEs) make up over 35% of the human genome and are classified as non-LTR retrotransposable elements. Among them, LINE1 is the predominant autonomous element, about 6 kb long, capable of making RNA copies, reverse transcribing, and integrating back into the genome, thereby influencing genomic stability. LINE1 activity is linked to genomic mutations, gene expression interference, and diseases such as hemophilia and certain cancers. This exploration provides insight into their lifecycle, functional mechanisms, and implications for human health.

Understanding Long Interspersed Nucleotide Elements (LINEs) and Their Role in the Human Genome - slide 1
01 / 12Understanding Long Interspersed Nucleotide Elements (LINEs) and Their Role in the Human Genome
1 / 17

Télécharger la présentation

Understanding Long Interspersed Nucleotide Elements (LINEs) and Their Role in the Human Genome
Une image / un lien ci-dessous est fourni (tel quel) pour télécharger la présentation

Politique de téléchargement : le contenu du site vous est fourni TEL QUEL pour votre information et votre usage personnel ; il ne peut être vendu, concédé sous licence ni partagé sur d’autres sites sans l’accord de son auteur.Le contenu vous est fourni TEL QUEL, pour votre information et votre usage personnel uniquement. Téléchargez la présentation en cliquant sur ce lien. Lors du téléchargement, si vous ne parvenez pas à télécharger une présentation, l’éditeur a peut-être supprimé le fichier de son serveur.Pendant le téléchargement, si vous ne parvenez pas à obtenir une présentation, le fichier a peut-être été supprimé par l’éditeur.

F I N

Plus de contenu associé

Transcription de la présentation

  1. Long Interspersed Nucleotide Elements (LINEs) Rami Al-Ouran

  2. Introduction • Transposable elements (TEs) occupy 46% of the human genome • Two classes of TEs: • DNA transposons • RNA transposons (retrotransposons or retroelements) • Retroelements: • Long terminal repeats (LTR) • non-LTR (LINE) • LINEs occupy over 35% of the human genome!!!

  3. Introduction • Non-LTR include: • Autonomous members: Long Interspersed Elements (LINE) • Non autonomous members: ALU, SINE • In mammals LINE1 is the predominant LINE element • TE activity leads to: • Genomic mutations • Interference with gene expression

  4. Definition of LINE1 • LINE1 is • an autonomous TE • about 6 kb long • that propagates in the genome by making RNA copies of themselves • and then reverse transcribed and integrated into the genome. • Encodes two open reading frames ORF1 and ORF2 required for L1 retransposition From Belancio et al., GenomeMedicine1:97, (2009)

  5. Structure of LINE1 5’UTR ORF1 ORF2 3’UTR 5’UTR that contains an internal promoter ORF1 which encodes protein ORF1p or p40 Inter-ORF linker region ORF2 which encodes ORF2p 3’UTR containing a functional polyadenylation signal

  6. Lifecycle of LINE1 From Belancio et al., GenomeMedicine1:97, (2009)

  7. L1 integration reaction. From Babushok et al. Human Mutation (2007)

  8. Lifecycle of LINE1 • Transcription. Initiation of transcription. • Before leaving the nucleus the number of of L1 transcripts can be reduced by RNA processing • Translation. L1 enters the cytoplasm for translation to produce ORF1 and ORF2 proteins are produced which are needed for retransposition. RNP(ribonucleoprotein particle) is formed • Insertion of new L1 copy. This could lead to DSB or to TPRT (Target Primed Reverse Transcription)

  9. LINE1 and Disease • Insertion of new element copies • In 1991 the discovery of first known active human L1 was from its retrotransposition into the factor VIII gene causing hemophilia • The random insertion process leads to diversity in gene diseases • In breast cancer BRCA1 and BRCA2 are disrupted by TE insertion • Interference with gene expression • Insertion of the retroelement disrupts the gene function and gene expression

  10. LINE1 and DSBs • Formation of DNA DSBs is associated with L1 expression • Depends on the enzymatic activity of the L1 ORF2 endonuclease domain

  11. Conclusions • LINEs are long interspersed retro elements • Account for almost 35% of human genome • LINE1 can cause human disease by insertion and modifying gene expression • LINE1 can lead to DSB

  12. References • Belancio VP, Deininger PL, Roy-Engel AM: LINE dancing in the human genome: transposable elements and disease. Genome Med. (2009) Oct 27;1(10):97. • Babushok, D. V. and Kazazian, H. H. (2007), Progress in understanding the biology of the human mutagen LINE-1. Human Mutation, 28: 527–539. doi: 10.1002/humu.20486