Meiosis entry during spermatogenesis requires reprogramming from mitotic to meiotic gene expression profiles. Transcriptional regulation has been extensively studied in meiosis entry, but gain of function for master transcription factors is insufficient to down-regulate mitotic genes. RNA helicase YTHDC2 and its partner MEIOC emerge as essential posttranscriptional regulators of meiotic entry. However, it is unclear what governs the RNA binding specificity of YTHDC2/MEIOC. Here, we identified RNA binding protein RBM46 as a component of the YTHDC2/MEIOC complex. Testis-specific
Rbm46
knockout in mice causes infertility with defective mitotic-to-meiotic transition, phenocopying global
Ythdc2
or
Meioc
knockout. RBM46 binds to 3′ UTR of mitotic transcripts within 100 nucleotides from YTHDC2 U-rich motifs and targets these transcripts for degradation. Dysregulated RBM46 expression is associated with human male fertility disorders. These findings establish the RBM46/YTHDC2/MEIOC complex as the major posttranscriptional regulator responsible for down-regulating mitotic transcripts during meiosis entry in mammalian spermatogenesis, with implications for understanding meiosis-related fertility disorders.
We describe a method for selective removal of caseins from milk. The method was developed as a model for transgenic milk processing. Raw cow milk spiked with nonmilk proteins was chosen as the model to resemble transgenic animal milk containing recombinant proteins. The most important elements of the process are (1) "deconstruction" of casein micelles in milk by destroying their Ca(2+) core using a chelating agent (EDTA), thus freeing any protein that might be entrapped in casein aggregates, and (2) "reconstruction" of micelles by providing them with a new Ca(2+) core, thus precipitating them away from the whey proteins, and the protein of interest. Calcium phosphate particles (CAP) were used to reform the disrupted casein micelles. The crystal clear supernatant fraction generated by this method provided >90% recovery and 6- to 13-fold concentration of the desired protein. Product-rich supernatant contained no detectable casein residues, as silver-stained SDS-PAGE and Western blot analyses demonstrated.
Intelligent hydrogels with excellent flexibility, biocompatibility, and stimulus responsivity can mimic the functions of the skin to detect human motions. However, the low mechanical strength limits its application in the field of biomimetic materials. In this work, polyacrylamide‐reduced graphene oxide (PAM‐rGO) composite hydrogels were prepared by the combination of PAM and partially rGO, and their biomimetic strain sensors were studied. The rGO played the role of “2D flexible crosslinking point” in the composite hydrogel. Through the H‐bonds between rGO and hydrogels, the toughness and strength of the composite hydrogel were enhanced. The maximum strain of the hydrogel changed from 751% to 1097%, and the maximum stress changed from 0.065 to 0.20 MPa. On the other hand, the interaction between the PAM backbone and the rGO provided a credible resistance response to the stimulation of strain. The better linear relationship between resistance and length was built, with R2 of 0.992. Furthermore, the composite hydrogels were assembled into wearable devices to monitor human‐motion, including fingers bending, elbows bending and walking. The experimental results showed that the PAM‐rGO composite hydrogel had great potential in the field of bionic skin.
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