CSB349H1 Lecture 12: Section 2- L12b
14 May 2018
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Lecture 12(b): piRNAs & LncRNAs
A. LncRNA H19 & Igf2 – miRNA Sponge
o LncRNA is maternally expressed | Igf2 is paternally expressed
o IMP1 is a gene that negatively regulates IGF2 expression, LncRNA H19 is capable
of controlling Igf2 expression by acting as a sponge for miRNA, let-7
§ miRNA let-7 regulates turnover of IMP1 transcripts by binding to 3’ UTR
o LncRNA H19 functions to reduce miRNA let-7 levels, therefore: ! level of IMP1
§ Higher level of IMP1 will reduce levels of Igf2
o If we knock-out H19 transcript: will have increased activity of miRNA let-7, therefore
a decrease level of IMP1 = ! Igf2 leading to overgrowth phenotype
B. LncRNA ELENA1 – Transcriptional Co-Regulator
o NRP1 are normally localized in the cytosol as a dimer
§ Upon pathogen infection dimer will undergo monomerization and
translocate to the nucleus, and will interact with TGA, a transcription factor
• TGA + NRP1 bind to promotor and induce expression of PR1 genes
o ELENA1, a LncRNA was found to be induced upon
pathogen infection via RNAseq
§ Knock-out of ELENA1 will lead to a decrease
expression of PR1 genes
§ Overexpression of ELENA1 will lead to an
increase expression of PR1 genes
Pathway:
o LncRNA can have functions as a scaffold:
§ Recruit mediator complex or subunits to the promotor site
• Will interact with transcription factors and mediate interaction with
further factors or proteins to induce transcription
C. LncRNA HOTAIR – Link to Cancer
o HOTAIR is encoded in the Hox C gene cluster and functions as a scaffold:
§ Brings together PRC2 and LSD1 to function together to silence Hox D gene
cluster by removing positive histone marks and adding negative histone marks to
induce heterochromatin formation
• PRC2 – functions to methylate H3K27 (negative histone mark)
• LSD1 – H3K4 specific demethylase (remove positive histone mark)
Inducing Cancer:
o If HOTAIR is expressed higher than normal levels it will become non-specific and
recruit the PRC2+LSD1 complex to other gene areas (i.e. metastasis suppressor genes)
which will become silenced, therefore HOTAIR contributing to cancer development
§ BRCA1 competes with HOTAIR for PRC2 – if mutated; there will be more
interaction with HOTAIR = more silencing of tumor suppressor gens
Document Summary
Lncrna h19 & igf2 mirna sponge, lncrna is maternally expressed | igf2 is paternally expressed. Lecture 12(b): pirnas & lncrnas: imp1 is a gene that negatively regulates igf2 expression, lncrna h19 is capable of controlling igf2 expression by acting as a sponge for mirna, let-7. Mirna let-7 regulates turnover of imp1 transcripts by binding to 3" utr: lncrna h19 functions to reduce mirna let-7 levels, therefore: level of imp1. Knock-out of elena1 will lead to a decrease expression of pr1 genes. Overexpression of elena1 will lead to an increase expression of pr1 genes. Pathway: lncrna can have functions as a scaffold: Inducing cancer: if hotair is expressed higher than normal levels it will become non-specific and recruit the prc2+lsd1 complex to other gene areas (i. e. metastasis suppressor genes) which will become silenced, therefore hotair contributing to cancer development. Brca1 competes with hotair for prc2 if mutated; there will be more interaction with hotair = more silencing of tumor suppressor gens.
