Deciphering the mRNP Code: RNA-Bound Determinants of Post-Transcriptional Gene Regulation

Gehring, Niels H.; Wahle, Elmar; Fischer, Utz

doi:10.1016/j.tibs.2017.02.004

Cited by 124 publications

(106 citation statements)

References 106 publications

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“…In this strand, some structural changes take place so that in some cases, the RNA molecule itself is a "finished product" that serves some important function within the cell. Often, however, transcription of an RNA molecule is followed by a translation step, which ultimately results in the production of a protein molecule [3][4][5].…”

Section: Gene Expression: An Overviewmentioning

confidence: 99%

“…The mRNA undergoes splicing of its regions to remove the non-coding parts of the transcript being the introns, so that only the coding sections being the exons remain. This part is called processing and right after this step, the final mRNA carries the information needed to code for proteins, which will transform into a functional protein [4,6,7].…”

Section: Gene Expression: An Overviewmentioning

confidence: 99%

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The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

et al. 2017

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Section: Gene Expression: An Overviewmentioning

confidence: 99%

Section: Gene Expression: An Overviewmentioning

confidence: 99%

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

et al. 2017

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“…Accordingly, RNA binding proteins (RBPs) are overrepresented in the proteome of these organisms in line with their role as the primary gene regulators. Such trans-regulatory RBPs dynamically bind to mRNA forming ribonucleoprotein complexes (mRNPs) that regulate the trafficking and processing of mRNA molecules from synthesis to decay [12]. Environmental pressures stimulate swift changes in mRNP localization, composition and function that accelerate rates of mRNA translation, decay, or sequestration to intracellular granules in response [13].…”

Section: Introductionmentioning

confidence: 99%

The mRNA-bound proteome ofLeishmania mexicana: novel genetic insight into an ancient parasite

Pablos

Ferreira

Dowle

et al. 2019

Preprint

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Leishmania parasite infections, termed the leishmaniases, cause significant global infectious disease burden. The lifecycle of the parasite embodies three main stages that require precise coordination of gene regulation to survive environmental shifts between sandfly and mammalian hosts. Constitutive transcription in kinetoplastid parasites means that gene regulation is overwhelmingly reliant on post-transcriptional mechanisms, yet strikingly few Leishmania trans-regulators are known. Utilizing optimised crosslinking and deep, quantified mass spectrometry, we present a comprehensive analysis of 1,400 mRNA binding proteins (mRBPs) and whole cell proteomes from the three main Leishmania lifecycle stages.Supporting the validity, while the crosslinked RBPome is magnitudes more enriched the protein identities of the crosslinked and non-crosslinked RBPomes were nearly identical.Moreover, multiple candidate RBPs were endogenously tagged and found to associate with discrete mRNA target pools in a stage-specific manner. Results indicate that in L.mexicana parasites, mRNA levels are not a strong predictor of the whole cell expression or RNA binding potential of encoded proteins. Evidence includes a low correlation between transcript and corresponding protein expression and stage-specific variation in protein expression versus RNA binding potential. Unsurprisingly, RNA binding protein enrichment correlates strongly with relative replication efficiency of the specific lifecycle stage. Our study is the first to quantitatively define and compare the mRBPome of multiple stages in kinetoplastid parasites. It provides novel, in-depth insight into the trans-regulatory mRNA:Protein (mRNP) complexes that drive Leishmania parasite lifecycle progression.

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“…RBPs mainly utilize RNA-binding domains such as RNA recognition motifs, the K Homology (KH) domain, and Zinc Finger motifs to interact with target mRNAs or with microRNAs (miRNAs) [3, 4]. Differential binding of RBPs to target RNAs determines the ability of these RBPs to modulate RNA processing, decay, localization, and translation [3]. Complementarity between regulatory RNAs and target RNAs also contributes to gene expression regulation.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA complementarity and target transcripts abundance

Zealy

Fomin

Davila

et al. 2018

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Eukaryotic mRNA metabolism regulates its stability, localization, and translation using complementarity with counter-part RNAs. To modulate their stability, small and long noncoding RNAs can establish complementarity with their target mRNAs. Although complementarity of small interfering RNAs and microRNAs with target mRNAs has been studied thoroughly, partial complementarity of long noncoding RNAs (lncRNAs) with their target mRNAs has not been investigated clearly. To address that research gap, our lab investigated whether the sequence complementarity of two lncRNAs, lincRNA-p21 and OIP5-AS1, influenced the quantity of target RNA expression. We predicted a positive correlation between lncRNA complementarity and target mRNA quantity. We confirmed this prediction using RNA affinity pull down, microarray, and RNA-sequencing analysis. In addition, we utilized the information from this analysis to compare the quantity of target mRNAs when two lncRNAs, lincRNA-p21 and OIP5-AS1, are depleted by siRNAs. We observed that human and mouse lincRNA-p21 regulated target mRNA abundance in complementarity-dependent and independent manners. In contrast, affinity pull down of OIP5-AS1 revealed that changes in OIP5-AS1 expression influenced the amount of some OIP5-AS1 target mRNAs and miRNAs, as we predicted from our sequence complementarity assay. Altogether, the current study demonstrates that partial complementarity of lncRNAs and mRNAs (even miRNAs) assist in determining target RNA expression and quantity.

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Deciphering the mRNP Code: RNA-Bound Determinants of Post-Transcriptional Gene Regulation

Cited by 124 publications

References 106 publications

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

The End of Snoring? Application of CRISPR/Cas9 Genome Editing for Sleep Disorders

The mRNA-bound proteome ofLeishmania mexicana: novel genetic insight into an ancient parasite

Long noncoding RNA complementarity and target transcripts abundance

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