RESUMEN
The heterogeneity of CARM1 controls first cell fate bias during early mouse development. However, how this heterogeneity is established is unknown. Here, we show that Carm1 mRNA is of a variety of specific exon-skipping splicing (ESS) isoforms in mouse two-cell to four-cell embryos that contribute to CARM1 heterogeneity. Disruption of paraspeckles promotes the ESS of Carm1 precursor mRNAs (pre-mRNAs). LincGET, but not Neat1, is required for paraspeckle assembly and inhibits the ESS of Carm1 pre-mRNAs in mouse two-cell to four-cell embryos. We further find that LincGET recruits paraspeckles to the Carm1 gene locus through HNRNPU. Interestingly, PCBP1 binds the Carm1 pre-mRNAs and promotes its ESS in the absence of LincGET. Finally, we find that the ESS seen in mouse two-cell to four-cell embryos decreases CARM1 protein levels and leads to trophectoderm fate bias. Our findings demonstrate that alternative splicing of CARM1 has an important role in first cell fate determination.
Asunto(s)
Empalme Alternativo , Embrión de Mamíferos , Proteína-Arginina N-Metiltransferasas , ARN Largo no Codificante , Animales , Empalme Alternativo/genética , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/citología , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Precursores del ARN/metabolismo , Precursores del ARN/genética , Regulación del Desarrollo de la Expresión Génica , Exones/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Desarrollo Embrionario/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
To obtain high-quality joints of Al/steel dissimilar materials, a new extrinsic-riveting friction stir lap welding (ERFSLW) method was proposed combining the synthesis advantages of mechanical riveting and metallurgical bonding. SiC-reinforced Al matrix composite bars were placed in the prefabricated holes in Al sheets and steel sheets, arranged in a zigzag array. The bars were stirred and mixed with Al sheets under severe plastic deformation (SPD), forming composite rivets to strengthen the mechanical joining. SiC particles were uniformly dispersed in the lower part of the welding nugget zone (WNZ). The smooth transition between the SiC mixed zone and extrinsic-riveting zone (ERZ) ensured the metallurgical bonding. The maximum tensile shear load of the joints reached 7.8 kN and the maximum load of the weld per unit length was 497 N/mm. The fracture occurred at the interface between the rivets and steel sheets rather than the conventional Al/steel joining interface. Moreover, ERFSLW can prolong the service life of joints due to three fracture stages. This method can be further extended to the welding of other dissimilar materials that conform to the model of "soft/hard".