SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal.
SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal.
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DOI：
10.1016/j.devcel.2022.01.011
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发表时间：
2022-03-14
影响因子：
11.8
通讯作者：
Klein OD
中科院分区：
文献类型：
--
作者：
Yu T;Cazares O;Tang AD;Kim HY;Wald T;Verma A;Liu Q;Barcellos-Hoff MH;Floor SN;Jung HS;Brooks AN;Klein OD
选择性剪接产生不同的mRNA变异，对发育、内稳态和更新是必不可少的。富含丝氨酸/精氨酸(SR)的剪接因子家族的蛋白质是器官发育以及细胞和生物体生存所广泛需要的主要剪接调节因子。然而，这些蛋白质如何支持成人器官功能在很大程度上仍不清楚。在这里，我们以持续生长的小鼠切牙为模型，剖析了典型的SR家族蛋白SRSF1在组织动态平衡和更新过程中的功能。我们确定了SRSF1控制的选择性剪接网络，它对于牙齿的增殖和祖细胞的存活是特别必要的，但对于分化细胞的生存是必不可少的。我们还观察到SRSF1在小肠上皮中类似的祖细胞特异性作用，表明SRSF1在成人上皮组织中具有保守的功能。因此，我们的发现定义了一种调节机制，通过该机制，SRSF1特异性地控制祖细胞特异性的选择性剪接事件，以支持成人组织的动态平衡和更新。周期祖细胞产生维持功能器官所需的终末分化细胞。Yu等人。在两个自我更新的组织，不断生长的小鼠切牙和小肠中，证明上皮祖细胞通过剪接因子SRSF1的几个靶标的适当剪接来维持。
Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR-family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal. Cycling progenitors generate the terminally differentiated cells needed to maintain a functional organ. Yu et al. demonstrate in two self-renewing tissues, the ever-growing mouse incisor and the small intestine, that epithelial progenitors are maintained through proper splicing of several targets of the splice factor SRSF1.
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影响因子：
16
作者：
Anczuków O;Akerman M;Cléry A;Wu J;Shen C;Shirole NH;Raimer A;Sun S;Jensen MA;Hua Y;Allain FH;Krainer AR
通讯作者：
Krainer AR
影响因子：
10.5
作者：
Hayakawa-Yano Y;Suyama S;Nogami M;Yugami M;Koya I;Furukawa T;Zhou L;Abe M;Sakimura K;Takebayashi H;Nakanishi A;Okano H;Yano M
通讯作者：
Yano M
影响因子：
23.9
作者：
Jadhav U;Saxena M;O'Neill NK;Saadatpour A;Yuan GC;Herbert Z;Murata K;Shivdasani RA
通讯作者：
Shivdasani RA
影响因子：
7
作者：
Brooks, Angela N.;Yang, Li;Graveley, Brenton R.
通讯作者：
Graveley, Brenton R.
影响因子：
64.8
作者：
Li, M;Indra, AK;Chambon, P
通讯作者：
Chambon, P