A coding-independent function of gene and pseudogene mRNAs regulates tumour biology
Laura Poliseno,Leonardo Salmena,Jiangwen Zhang,Brett S. Carver,William J. Haveman,Pier Paolo Pandolfi +5 more
TLDR
It is found that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role, and this analysis extended to other cancer-related genes that possess pseudogenes, and revealed a non-coding function for mRNAs.Abstract:
The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs could possess a regulatory role that relies on their ability to compete for microRNA binding, independently of their protein-coding function. As a model for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene PTENP1 and the critical consequences of this interaction. We find that PTENP1 is biologically active as it can regulate cellular levels of PTEN and exert a growth-suppressive role. We also show that the PTENP1 locus is selectively lost in human cancer. We extended our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. We also demonstrate that the transcripts of protein-coding genes such as PTEN are biologically active. These findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.read more
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Circular RNAs are a large class of animal RNAs with regulatory potency
Sebastian Memczak,Marvin Jens,Antigoni Elefsinioti,Francesca Torti,Janna Krueger,Agnieszka Rybak,Luisa Maier,Sebastian D. Mackowiak,Lea H. Gregersen,Mathias Munschauer,Alexander Loewer,Ulrike Ziebold,Markus Landthaler,Christine Kocks,Ferdinand le Noble,Nikolaus Rajewsky +15 more
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Journal ArticleDOI
Natural RNA circles function as efficient microRNA sponges
Thomas B. Hansen,Trine I. Jensen,Bettina Hjelm Clausen,Jesper B. Bramsen,Bente Finsen,Christian Kroun Damgaard,Jørgen Kjems +6 more
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Journal ArticleDOI
A ceRNA Hypothesis: The Rosetta Stone of a Hidden RNA Language?
TL;DR: It is proposed that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer.
Journal ArticleDOI
GENCODE: The reference human genome annotation for The ENCODE Project
Jennifer Harrow,Adam Frankish,José M. González,Electra Tapanari,Mark Diekhans,Felix Kokocinski,Bronwen Aken,Daniel Barrell,Amonida Zadissa,Stephen M. J. Searle,If H. A. Barnes,Alexandra Bignell,Veronika Boychenko,Toby Hunt,M. Kay,Gaurab Mukherjee,Jeena Rajan,Gloria Despacio-Reyes,Gary Saunders,Charles A. Steward,Rachel A. Harte,Michael F. Lin,Cédric Howald,Andrea Tanzer,Thomas Derrien,Jacqueline Chrast,Nathalie Walters,Suganthi Balasubramanian,Baikang Pei,Michael L. Tress,Jose Manuel Rodriguez,Iakes Ezkurdia,Jeltje Van Baren,Michael R. Brent,David Haussler,Manolis Kellis,Alfonso Valencia,Alexandre Reymond,Mark Gerstein,Roderic Guigó,Tim Hubbard +40 more
TL;DR: This work has examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites, and over one-third of GENCODE protein-Coding genes aresupported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas.
Journal ArticleDOI
Molecular Mechanisms of Long Noncoding RNAs
Kevin C. Wang,Howard Y. Chang +1 more
TL;DR: These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution.
References
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Journal ArticleDOI
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TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Journal ArticleDOI
Real-time quantification of microRNAs by stem–loop RT–PCR
Caifu Chen,Dana Ridzon,Adam Broomer,Zhaohui Zhou,Danny H. Lee,Julie T. Nguyen,Maura Barbisin,Nan Lan Xu,Vikram R. Mahuvakar,Mark R. Andersen,Kaiqin Lao,Kenneth J. Livak,Karl J. Guegler +12 more
TL;DR: A novel microRNA quantification method has been developed using stem–loop RT followed by TaqMan PCR analysis, which enables fast, accurate and sensitive miRNA expression profiling and can identify and monitor potential biomarkers specific to tissues or diseases.
Journal ArticleDOI
Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals
Mitchell Guttman,Ido Amit,Manuel Garber,Courtney French,Michael F. Lin,David M. Feldser,Maite Huarte,Maite Huarte,Or Zuk,Bryce W. Carey,John P. Cassady,Moran N. Cabili,Rudolf Jaenisch,Tarjei S. Mikkelsen,Tyler Jacks,Nir Hacohen,Bradley E. Bernstein,Bradley E. Bernstein,Manolis Kellis,Manolis Kellis,Aviv Regev,John L. Rinn,John L. Rinn,John L. Rinn,Eric S. Lander +24 more
TL;DR: It is demonstrated that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFκB, Sox2, Oct4 (also known as Pou5f1) and Nanog, defining a unique collection of functional linc RNAs that are highly conserved and implicated in diverse biological processes.