Long non-coding RNAs Flashcards
What does the % of non-coding DNA correlate with?
DNA compexity
What is considered as a long non-coding RNA?
bigger than 200bp
How are lncRNAs expressed?
In a more tissue/ cell-type specific manner than protein coding genes: they have fewer alternative splicing events
Arrangements of lncRNA
- Divergent
- Sense
- Intergenic
- Antisense
- Intronic
Divergent lncRNA
lncRNA share the same promoter with the protein- coding gene but are transcribed in the opposite direction
Sense lncRNA
the long non-coding transcription unit is inside the transcription unit of the protein-coding genes and the direction is the same
Intergenic lncRNA
Long non-coding is located in the genomic space between 2 protein- coding genes
Antisense lncRNA
long non-coding starts to be transcribed in the end of the protein- coding genes and this transcription gets in the opposite direction
Intronic lncRNA
Non-coding RNAs whom transcription unit is inside one protein coding gene
Ways lncRNA are expressed in the nucleus
- Scaffold for complex formation
- Controlled recruitment of TRs
- Regulation of splicing
- Regulation of chromosome looping
- Formation and function of subnuclear structures
Ways lncRNA are expressed in the cytoplasm
- Control of translation rate
- Control of mRNA decay
- miRNA sequestration
Control of translation rate
by binding to to mRNA in the cytoplasm they can activate/repress translation
Control of mRNA decay
By recognising specific targets and recruiting/preventing the recruitment of nucleases of the target RNA
miRNA sequestration
Can regulate other non-coding RNAs such as miRNA. When there is a high level of non-coding, the miRNA will bind to lncRNAs instead of mRNA and miRNA is inhibited: increased translation
Controlled recruitment of TRs
lncRNAs can directly regulate recruitment of TRs
Scaffold for complex formation
Many proteins recognise lncRNAs and may promote the formation of CRCs, regulating the reposition of histone modifications –> affecting gene expression
Regulation of splicing
can interact with splicing factors and recruit splicing factors with particular locations on the mRNA
Formation and function of subnuclear structures
lncRNAs can promote the formation of some nuclear structures
Regulation of chromosome looping
Bridge promoters to enhancers to regulate the activation of gene expression
lncRNA post-transcriptional modification
- Adenosine N-6 methylation
- Adenosine deamination to inosine
- Uridine isomerisation to 5-ribosyluracil
- 5- methylcytidine
What can the post-transcriptional modifications cause?
Change the affinity of a protein that recognsies the RNA
Effects of mutations in lncRNAs
- eQTL: mutation in a region in lncRNAs causing the creation of a binding site of a transcription activator:- may cause expression of lncRNAs in tissues where it should not be expressed
- Mutations causing exon skipping
- Mutations in secondary structure
What can lncRNAs be used for?
biomarker to perform diagnosis of the disease; works well as they have a restricted pattern of disease
Enhancer eRNAs
cis-regulatory sequences that recruit transcription factors
How do eRNAs work?
loop in proximity of the promoter and remodel its activity by promoting/repressing the recruitment of general transcription machinery
Mechanisms of how eRNAs target gene expression?
- Direct role in the control of the transcriptional role by building the lopp between the enhancer and the promoter
- Mediate the interactions of TFs with cofactors
- Deposition of histone marks
- Facilitate RNA pol II transition to elongation
