CircRNAs Are Here to Stay: A Perspective on the MLL Recombinome

Frontiers in Genetics
Anna Dal MolinStefania Bortoluzzi

Abstract

Chromosomal translocations harbored by cancer genomes are important oncogenic drivers. In MLL rearranged acute leukemia (MLLre) MLL/KMT2A fuses with over 90 partner genes. Mechanistic studies provided clues of MLL fusion protein leukemogenic potential, but models failed to fully recapitulate the disease. Recently, expression of oncogenic fusion circular RNAs (f-circ) by MLL-AF9 fusion was proven. This discovery, together with emerging data on the importance and diversity of circRNAs formed the incentive to study the circRNAs of the MLL recombinome. Through interactions with other RNAs, such as microRNAs, and with proteins, circRNAs regulate cellular processes also related to cancer development. CircRNAs can translate into functional peptides too. MLL and most of the 90 MLL translocation partners do express circRNAs and exploration of our RNA-seq dataset of sorted blood cell populations provided new data on alternative circular isoform generation and expression variability of circRNAs of the MLL recombinome. Further, we provided evidence that rearrangements of MLL and three of the main translocation partner genes can impact circRNA expression, supported also by preliminary observations in leukemic cells. The emerging picture und...Continue Reading

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Citations

Jul 18, 2020·Frontiers in Molecular Biosciences·Olivia Perez de AchaMyriam Gorospe
Oct 30, 2019·International Journal of Oncology·Katherine L HarperAdrian Whitehouse
Oct 19, 2020·Journal of Hematology & Oncology·Xiangxiang ZhouXin Wang
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Anna Dal MolinStefania Bortoluzzi
Nov 9, 2021·JCI Insight·Loelia BabinFabienne Meggetto

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Datasets Mentioned

BETA
GSE110159

Methods Mentioned

BETA
RNA-seq

Software Mentioned

CirComPara
Findcirc
CIRCexplorer2

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