How cells get the message: dynamic assembly and function of mrna–protein complexes

KEY POINTS * Global approaches are defining the full complement of proteins with RNA-binding capacity in living cells. * RNA packaging by proteins begins during transcription and determines

the fate of the RNA. * RNA-binding proteins (RBPs) can act as 'molecular rulers', sorting RNAs according to their length. * RBPs can link sequential and non-sequential processing

steps. * A future challenge is to define the composition of individual mRNPs at different stages of remodelling. ABSTRACT mRNA is packaged into ribonucleoprotein particles called mRNPs. A

multitude of RNA-binding proteins as well as a host of associated proteins participate in the fate of mRNA from transcription and processing in the nucleus to translation and decay in the

cytoplasm. Methodological innovations in cell biology and genome-wide high-throughput approaches have revealed an unexpected diversity of mRNA-associated proteins and unforeseen

interconnections between mRNA-processing steps. Recent insights into mRNP formation _in vivo_ have also highlighted the importance of mRNP packaging, which can sort RNAs on the basis of

their length and determine mRNA fate through alternative mRNP assembly, processing and export pathways. Access through your institution Buy or subscribe This is a preview of subscription

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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NUCLEAR MRNA DECAY: REGULATORY NETWORKS

THAT CONTROL GENE EXPRESSION Article 18 April 2024 MRNA RECOGNITION AND PACKAGING BY THE HUMAN TRANSCRIPTION–EXPORT COMPLEX Article 05 April 2023 CYTOPLASMIC MRNA DECAY AND QUALITY CONTROL

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proteins for TAP-dependent mRNA export. _Mol. Cell_ 11, 837–843 (2003). CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We thank members of our laboratory, T. Pederson and

F. McNicoll for helpful discussions and comments on the manuscript. Work in our laboratory on mRNPs is supported by funding from the Max Planck Society and the German Research Foundation

(NE-909/3-1 to K.M.N.), and long-term postdoctoral fellowships from the European Molecular Biology Organization (EMBO) and Fonds de recherche en santé du Québec (FRSQ; to M.M.-M.). AUTHOR

INFORMATION AUTHORS AND AFFILIATIONS * Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307, Dresden, Germany Michaela Müller-McNicoll & Karla M.

Neugebauer Authors * Michaela Müller-McNicoll View author publications You can also search for this author inPubMed Google Scholar * Karla M. Neugebauer View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Michaela Müller-McNicoll or Karla M. Neugebauer. ETHICS DECLARATIONS COMPETING INTERESTS The authors

declare no competing financial interests. RELATED LINKS FURTHER INFORMATION Karla M. Neugebauer's homepage POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2

POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 GLOSSARY * Messenger ribonucleoprotein particles (mRNPs). Complexes composed of mature mRNAs bound by various RNA-binding proteins and

associated proteins recruited via protein–protein interactions. The formation of mRNPs allows proper packaging of the mRNA, which is essential for efficient nuclear export. * 5′ end capping

As soon as a nascent transcript emerges from RNA polymerase II during transcription, it is capped at its 5′ end. This 7-methylguanosine cap (m7G cap) protects the mRNA from degradation and

is essential for its translation. * Peptidyl-prolyl-isomerases (PPIs). A group of metabolic enzymes that catalyse the _cis_–_trans_ isomerization of peptide bonds in polypeptide chains. PPIs

have important roles in the folding of newly synthesized proteins but were recently shown also to bind mRNAs. * RNA recognition motif (RRM). One of the most abundant RNA-binding domains in

eukaryotes. * Spliceosome A ribonucleoprotein complex that is responsible for splicing nuclear precursor mRNA (pre-mRNA). It is composed of five small nuclear ribonucleoproteins (snRNPs) and

more than 50 non-snRNP proteins, which recognize and assemble on exon–intron boundaries to catalyse intron removal from the precursor mRNA (pre-mRNA). * Dicer An RNase III family

endonuclease that processes double-stranded RNA and precursor microRNAs into small interfering RNAs and microRNAs, respectively. * Heterogeneous nuclear ribonucleoprotein particles (hnRNPs).

Complexes of newly synthesized precursor mRNA (pre-mRNA) and RNA-binding proteins, known as heterogeneous ribonucleoproteins, which form during transcription in the cell nucleus. The

abundant hnRNP proteins regulate splicing and mark the RNA as immature. After splicing has occurred, the hnRNP proteins mainly remain bound to spliced introns. * Premature cleavage and

polyadenylation (PCA). Misprocessing of precursor mRNAs (pre-mRNA) by the cleavage and polyadenylation machinery. Truncated transcripts arise through the use of cryptic or inappropriate

polyadenylation signals present at the 5′ end or within introns of the pre-mRNA. * R loops Hybrid structures consisting of RNA and DNA in which RNA displaces a DNA strand to hybridize to its

complementary DNA sequence. * Exon junction complex (EJC). A protein complex that is deposited ~24 nucleotides upstream of the exon–exon junctions of newly synthesized, spliced mRNAs. The

EJC contains four core proteins — eukaryotic initiation factor 4AIII (EIF4AIII), Y14, mago nashi homologue (MAGOH) and Barentsz (BTZ) — and several loosely associated proteins. * SR proteins

Evolutionarily conserved RNA-binding proteins with essential functions in precursor mRNA (pre-mRNA) splicing in metazoans. Individual SR proteins have distinct RNA-binding capacities and

are important regulators of alternative splicing, while some also function in post-splicing steps of gene expression. * Balbiani ring Chromosome puffs or large diffused uncoiled regions,

which are the sites of RNA transcription, in the giant polytene chromosomes of _Chironomus tentans_ salivary gland cells. * Exosome A protein complex that has 3′ to 5′ exonuclease activity

(although an endonuclease activity has also been described). Two forms of the exosome have been characterized that differ in their associated cofactors and cellular localization (one is

nuclear and one is cytoplasmic). * Promoter upstream non-coding transcripts (PROMPTs). A recently discovered class of human RNAs. PROMPTs are produced upstream of promoters of active

protein-coding genes. They are mainly nuclear and have poly(A) tails and 5′ cap structures. * Nonsense-mediated mRNA decay (NMD). The process by which mRNAs containing premature termination

codons are destroyed to preclude the production of truncated and potentially deleterious protein products. It is also used in combination with specific alternative splicing events to control

the levels of some proteins. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Müller-McNicoll, M., Neugebauer, K. How cells get the message: dynamic

assembly and function of mRNA–protein complexes. _Nat Rev Genet_ 14, 275–287 (2013). https://doi.org/10.1038/nrg3434 Download citation * Published: 12 March 2013 * Issue Date: April 2013 *

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