POU5F1 (OCT4), SOX2, NANOG 抑制与分化相关的基因
中文名称
通路描述
POU5F1 (OCT4), SOX2 和 NANOG 结合靶基因启动子上的元件。每个转录因子的靶基因重叠广泛：POU5F1、SOX2 和 NANOG 共同占据至少 353 个基因（Boyer et al. 2005）。约一半的 POU5F1 靶基因也结合 SOX2，而约 90% 的这些靶基因也结合 NANOG（Boyer et al. 2005）。当转录因子结合后，激活核心转录网络中单一种类靶基因的转录，并抑制另一种单一种类（Kim et al. 2006, Matoba et al. 2006, Player et al. 2006, Assou et al. 2007, Babaie et al. 2007, Chavez et al. 2009, Jung et al. 2010）。本模块列出的靶基因是被抑制的基因。从小鼠干细胞推断人类干细胞时需小心，因为两者之间存在显著差异（Ginis et al. 2004）。
英文描述
tRNA-derived small RNA (tsRNA or tRNA-related fragment, tRF) biogenesis Defined fragments of tRNAs, termed tRNAâderived small RNAs (tsRNAs), have been observed in particular cell types and in response to biological conditions such as exposure to sex hormone or stresses such as hypoxia, starvation, oxidative stress, and virus infection (reviewed in Keam and Hutvagner 2015, Kumar et al. 2016, Oberbauer and Schaefer 2018, Park et al. 2020, Su et al. 2020, Xie et al. 2020, Zhu et al. 2020). Rather than being the random products of tRNA degradation, tsRNAs appear to be the specific products of ribonucleases. Two categories of tRNAâderived small RNAs (tsRNAs) have been described: (1) longer (31â40nt) tsRNAs known as tRNA halves or stressâinduced tsRNAs (tiRNAs) that are produced by single cleavage of tRNAs within or near the anticodon and (2) shorter (15â30 nt) tsRNAs termed tRNA-related fragments (tRFs) that result from cleavage closer to the 5' or 3' end of the tRNA. tRF-3s are derived from the 3' region of the tRNA, approximately the region from the T loop to the 3' terminus. tRF-5s are derived from the 5' region of the tRNA, approximately the region from the D loop to the 5' terminus. tRF2âtype tRFs (also called internal tRFs) are derived from the central region of the tRNA, approximately the region between the D loop and the T loop and containing the anticodon. tRF-1s, also known as Type II tRFs or 3âU tRFs, are the 3' trailers of particular tRNAs that persist after processing.
In most cases the enzymes responsible for the cleavages are not yet known, however several ribonucleases involved in cleavage of tRNA have been identified: the secreted and endocytosed ribonuclease A family members angiogenin (ANG) and RNase 1; the interferon-induced ribonucleases RNase L, Schlafen 11 (SLFN11) and Schlafen13 (SLFN13 or RNase S13); the cytosolic ribonuclease IIIâlike (double strand RNAâspecific) enzyme DICER1; and the RNA processing enzyme ELAC2. ANG is secreted, binds receptors on cell membranes, is endocytosed, and translocates to the nucleus. ANG cleaves within the anticodon loop to produce tRNA halves and the cleavage is thought to occur while ANG is transiently located in the cytosol (Lee and Vallee 1989, Saxena et al. 1992, Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). Cleavage by ANG is observed in response to cellular stresses such as starvation (Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). However, ANG knockout cells continue to produce stress-induced tRNA halves, suggesting that other enzymes are also involved in producing the halves (Su et al. 2019). Similar to ANG as an RNase A member, the secreted endoribonuclease RNase 1 cleaves tRNAs at the anticodon loop in the extracellular space (Nechooshtan et al. 2020).
Interferon-induced RNases can also cleave tRNAs. RNase L is responsive to double stranded RNAs and cleaves at the tRNA anticodon loop (Donovan et al. 2017). Schlafen family members SLFN11 and SLFN13 can also cleave tRNAs (Li et al. 2018, Yang et al. 2018).
DICER1 cleaves doubleâstranded regions of tRNAs near the 5' terminus or 3' terminus to produce short tRFs (Cole et al. 2009, Yeung et al. 2009, Maute et al. 2013, Hasler et al. 2016). The mechanism that dissociates the doubleâstranded products of DICER1 to yield singleâstranded tRFs may be the same as that for miRNAs, but this has not yet been demonstrated. Furthermore, the bulk of the short tRFs is still detected in DICER1-null cells (Kumar 2014, Kuscu & Kumar et al. 2018), suggesting other unknown factors are involved in their biogenesis. ELAC2 in the cytosol cleaves the 3' trailers of precursors of tRNA Ser TGA, tRNA Ser GTC, and tRNA Asp GTC, and tRNA Asp GTC (Lee et al. 2009). The trailers (also called tRF-1s) then persist in the cytosol (Kumar et al. 2014).
In most cases the enzymes responsible for the cleavages are not yet known, however several ribonucleases involved in cleavage of tRNA have been identified: the secreted and endocytosed ribonuclease A family members angiogenin (ANG) and RNase 1; the interferon-induced ribonucleases RNase L, Schlafen 11 (SLFN11) and Schlafen13 (SLFN13 or RNase S13); the cytosolic ribonuclease IIIâlike (double strand RNAâspecific) enzyme DICER1; and the RNA processing enzyme ELAC2. ANG is secreted, binds receptors on cell membranes, is endocytosed, and translocates to the nucleus. ANG cleaves within the anticodon loop to produce tRNA halves and the cleavage is thought to occur while ANG is transiently located in the cytosol (Lee and Vallee 1989, Saxena et al. 1992, Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). Cleavage by ANG is observed in response to cellular stresses such as starvation (Fu et al. 2009, Yamasaki et al. 2009, Emara et al. 2010, Ivanov et al. 2011). However, ANG knockout cells continue to produce stress-induced tRNA halves, suggesting that other enzymes are also involved in producing the halves (Su et al. 2019). Similar to ANG as an RNase A member, the secreted endoribonuclease RNase 1 cleaves tRNAs at the anticodon loop in the extracellular space (Nechooshtan et al. 2020).
Interferon-induced RNases can also cleave tRNAs. RNase L is responsive to double stranded RNAs and cleaves at the tRNA anticodon loop (Donovan et al. 2017). Schlafen family members SLFN11 and SLFN13 can also cleave tRNAs (Li et al. 2018, Yang et al. 2018).
DICER1 cleaves doubleâstranded regions of tRNAs near the 5' terminus or 3' terminus to produce short tRFs (Cole et al. 2009, Yeung et al. 2009, Maute et al. 2013, Hasler et al. 2016). The mechanism that dissociates the doubleâstranded products of DICER1 to yield singleâstranded tRFs may be the same as that for miRNAs, but this has not yet been demonstrated. Furthermore, the bulk of the short tRFs is still detected in DICER1-null cells (Kumar 2014, Kuscu & Kumar et al. 2018), suggesting other unknown factors are involved in their biogenesis. ELAC2 in the cytosol cleaves the 3' trailers of precursors of tRNA Ser TGA, tRNA Ser GTC, and tRNA Asp GTC, and tRNA Asp GTC (Lee et al. 2009). The trailers (also called tRF-1s) then persist in the cytosol (Kumar et al. 2014).
所含基因
3 个基因