Exploring Translational Control of Maternal mRNAs in Zebrafish

Winata, Cecilia Lanny; Łapiński, Maciej; Ismail, Hisyam M; Mathavan, Sinnakaruppan; Sampath, Prabha

doi:10.1007/978-1-0716-0970-5_29

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…These interactions are key in regulating RNA stability and translation in changing cellular conditions (Lopez de Silanes et al ., 2004). In early zebrafish embryos, 3’UTR elements and translational control play crucial roles in regulation and stability of maternal RNAs (Mishima and Tomari, 2016; Winata et al ., 2021). Mammalian studies also identified general motifs via CLIP-seq that some RBPs bind to, for instance: UGAU, AAUAAA.…”

Section: Discussionmentioning

confidence: 99%

Translational control offurinaby an RNA regulon is essential for heart morphogenesis and cardiac valve function

Nagorska¹,

Lambert²,

Inman³

et al. 2023

Preprint

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Heart development is a complex process, starting from specification of cardiac precursors and formation of a linear tube to gradual progression to a functional beating organ. For normal heart development, many processes, including asymmetric positioning of the heart along the left-right (L/R) axis, cardiac growth, and cardiac valve morphogenesis must be completed successfully. Although heart development has been studied extensively, the mechanisms that control heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA is a key protein that functions in heart development in many vertebrates including zebrafish. How FurinA activity is regulated during heart development is not known. Through computational analysis of the zebrafish transcriptome, we identified a short sequence and structure RNA motif in a variant transcript of FurinA harbouring a long 3′ untranslated region (3′UTR). The alternative 3′UTR furina isoform is expressed at embryonic stages preceding organ positioning. Reporter localization and RNA-binding assays show that the furina 3′UTR forms complexes with the conserved RNA-binding protein and translational repressor Ybx1. Conditional mutant zebrafish embryos affecting ybx1 show premature and increased Furin reporter protein expression, abnormal cardiac morphogenesis and heart looping defects. Our mutant ybx1 hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and many mutant embryos show retrograde blood flow from the ventricle to the atrium. This is similar to human heart valve regurgitation patients. Our findings show an essential function for the 3′UTR element/Ybx1 regulon in translational repression of FurinA, revealing a new upstream regulatory mechanism that controls embryonic heart development, and demonstrates the ybx1 mutant as a model to study cardiac valve development and function.

show abstract

Section: Discussionmentioning

confidence: 99%

Translational control offurinaby an RNA regulon is essential for heart morphogenesis and cardiac valve function

Nagorska¹,

Lambert²,

Inman³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…These interactions are key in regulating RNA stability and translation in changing cellular conditions ( Lopez de Silanes et al, 2004 ). In early zebrafish embryos, 3′UTR elements and translational control play crucial roles in regulation and stability of maternal RNAs ( Mishima and Tomari, 2016 ; Winata et al, 2021 ). Mammalian studies have also identified general motifs via CLIP-seq (cross-linking immunoprecipitation sequencing) that some RBPs bind to, for instance: UGAU, AAUAAA.…”

Section: Discussionmentioning

confidence: 99%

Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function

Nagorska,

Zaucker,

Lambert

et al. 2023

Development

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Heart development is a complex process that requires asymmetric positioning of the heart, cardiac growth and valve morphogenesis. The mechanisms controlling heart morphogenesis and valve formation are not fully understood. The pro-convertase FurinA functions in heart development across vertebrates. How FurinA activity is regulated during heart development is unknown. Through computational analysis of the zebrafish transcriptome, we identified an RNA motif in a variant FurinA transcript harbouring a long 3′ untranslated region (3′UTR). The alternative 3′UTR furina isoform is expressed prior to organ positioning. Somatic deletions in the furina 3′UTR lead to embryonic left-right patterning defects. Reporter localisation and RNA-binding assays show that the furina 3′UTR forms complexes with the conserved RNA-binding translational repressor, Ybx1. Conditional ybx1 mutant embryos show premature and increased Furin reporter expression, abnormal cardiac morphogenesis and looping defects. Mutant ybx1 hearts have an expanded atrioventricular canal, abnormal sino-atrial valves and retrograde blood flow from the ventricle to the atrium. This is similar to observations in humans with heart valve regurgitation. Thus, the furina 3′UTR element/Ybx1 regulon is important for translational repression of FurinA and regulation of heart development.

show abstract

Exploring Translational Control of Maternal mRNAs in Zebrafish

Cited by 2 publications

References 23 publications

Translational control offurinaby an RNA regulon is essential for heart morphogenesis and cardiac valve function

Translational control offurinaby an RNA regulon is essential for heart morphogenesis and cardiac valve function

Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function

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