RT Journal Article
SR Electronic
T1 RNA-Dependent Amplification of Mammalian mRNA Encoding Extracellular Matrix Components: Identification of Chimeric RNA Intermediates for α1, β1, and γ1 Chains of Laminin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 376293
DO 10.1101/376293
A1 Vladimir Volloch
A1 Sophia Rits
A1 Bjorn Olsen
YR 2018
UL http://biorxiv.org/content/early/2018/12/05/376293.abstract
AB The aim of the present study was to test for the occurrence of key elements predicted by the previously postulated mammalian RNA-dependent mRNA amplification model in a tissue producing massive amounts of extracellular matrix proteins. At the core of RNA-dependent mRNA amplification, until now only described in one mammalian system, is the self-priming of an antisense strand and extension of its 3’ terminus into a sense-oriented RNA containing the protein-coding information of a conventional mRNA. The resulting product constitutes a new type of biomolecule. It is chimeric in that it contains covalently connected antisense and sense sequences in a hairpin configuration. Cleavage of this chimeric intermediate in the loop region of a hairpin structure releases mRNA which contains an antisense segment in its 5’UTR; depending on the position of self-priming, the chimeric end product may encode the entire protein or its C-terminal fragment. The occurrence of such composite chimeric molecules is unique for this type of mRNA amplification and represents a conclusive “identifier” of this process. We report here the detection, by next generation sequencing, of such chimeric junction sequences for mRNAs molecules encoding αl, β1, and γ1 chains of laminin in cells of the extracellular matrix-generating Engelbreth-Holm-Swarm (EHS) mouse tumor, best known for producing extraordinarily large amounts of “Matrigel”.