ライフサイエンスコーパス: hnRNP L

1 hnRNP L and NF90 were found to associate with HCV RNA in

2 hnRNP L binds to this ARS motif and regulates ARS-contai

3 hnRNP L undergoes two previously unrecognized, condition

4 hnRNP L was found to associate with both the mRNA export

5 contrast to its direct repression of exon 4, hnRNP L represses exon 5 by countering the activity of a

6 In addition, hnRNP L(-/-) thymocytes express aberrant levels of the C

7 eported that competition between miR-297 and hnRNP L to bind a 3UTR-localized CA-rich element (CARE)

8 rong correlation between hnRNP L binding and hnRNP L-dependent splicing regulation.

9 PCBP2, IGF2BP1, and hnRNP L binding were blocked by preannealing the single-

10 PCBP2, IGF2BP1, and hnRNP L bound single-stranded RNA, while DHX9, ADAR1, an

11 between miR-574-3p, a CA-rich microRNA, and hnRNP L.

12 It is proposed that PTB and hnRNP L are positive regulators of Cat-1 mRNA translatio

13 he protective RNA binding proteins PTBP1 and hnRNP L to preferentially bind and down-regulate transcr

14 The interaction between the APE1 and hnRNP-L proteins does not require the presence of nCaRE-

15 r ribonucleoprotein L (HNRNPL, also known as hnRNP L).

16 by additional RNA-binding proteins, such as hnRNP L, PTB/nPTB and hnRNP A1/A2.

17 SETD2, by interacting with Pol II as well as hnRNP L, can mediate the crosstalk between the transcrip

18 ecifically show a strong correlation between hnRNP L binding and hnRNP L-dependent splicing regulatio

19 we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2.

20 positive correlation existed between binding hnRNP L and enhancement of intronless beta-globin gene e

21 side chains in hydrophobic pockets formed by hnRNP L RRM2.

22 gether, our data indicate that protection by hnRNP L overrides the presence of multiple 3'UTR introns

23 creased Itga2 pre-mRNA splicing regulated by hnRNP L and depends on CA repeat length at a specific si

24 ntly, analysis of several exons regulated by hnRNP L shows a clear relationship between the potential

25 RNP L further, we have generated conditional hnRNP L knockout mice and found that LckCre-mediated del

26 574-3p, acting as a decoy, binds cytoplasmic hnRNP L and prevents its binding to the CARE and stimula

27 In the absence of the enhancer, hnRNP L unexpectedly activates exon inclusion.

28 The RNA processing factor hnRNP L is required for T cell development and function.

29 t the target motifs for the splicing factors hnRNP-L, PTB, and PCBP that are up-regulated in infant l

30 erogeneous nuclear ribonucleoprotein family (hnRNP L, hnRNP A1, and hnRNP M) were identified.

31 Further, we found hnRNP L, hnRNP A1, and hnRNP A2B1 bind UNC13A RNA and re

32 and regulates ARS-containing exons; however, hnRNP L does not function alone.

33 Here, we identify hnRNP L as a factor that protects mRNAs with NMD-inducin

34 d several novel proteins, including IGF2BP1, hnRNP L, DHX9, ADAR1, and NF90 (ILF3).

35 By UV crosslinking and immunoprecipitation, hnRNP L binds more avidly to CA21, relative to CA6.

36 feration rates of double-negative 4 cells in hnRNP L(-/-) mice.

37 L to the cytoplasm, which markedly increases hnRNP L binding to VEGFA mRNA thereby inhibiting miRNA a

38 We describe a novel HILDA (hypoxia-inducible hnRNP L-DRBP76-hnRNP A2/B1) complex that coordinates a t

39 nuclear ribonuclear protein family member L (hnRNP L), a member of the hnRNP family of RNA processing

40 s heterogeneous nuclear ribonucleoprotein L (hnRNP L) by protein sequencing.

41 finity of heterogeneous ribonucleoprotein L (hnRNP L) for a 6 CA repeat sequence (CA6) within intron

42 Heterogeneous nuclear ribonucleoprotein L (hnRNP L) interacted with this ESS, and downregulation of

43 , heterogeneous nuclear ribonucleoprotein L (hnRNP L), promote the efficient translation of Cat-1 mRN

44 t heterogeneous nuclear ribonucleoprotein L (hnRNP L), which also binds the VEGFA 3'-UTR CARE, preven

45 g heterogeneous nuclear ribonucleoprotein L (hnRNP L).

46 e heterogeneous nuclear ribonucleoprotein L (hnRNP-L).

47 actors 9G8 and SRp20, DNA-methyltransferase, hnRNP L, and hnRNP U.

48 Hypoxia induces translocation of nuclear hnRNP L to the cytoplasm, which markedly increases hnRNP

49 g in resting T cells through the activity of hnRNP L and confers activation-induced exon skipping in

50 hus, we propose that specific association of hnRNP L with VEGF mRNA under hypoxia may play an importa

51 The associations of hnRNP L and PSF with the ESS1 complex are largely indepe

52 in vitro mRNA splicing, decreased binding of hnRNP L results in decreased splicing efficiency and an

53 Remarkably, binding of hnRNP L to an exon represses strong splice sites but enh

54 Binding of hnRNP L to the IRES or the Cat-1 mRNA in vivo was indepe

55 Deletion of hnRNP L also blocked the migration and egress of single-

56 CRISPR/Cas9 deletion of hnRNP L binding sites near the BCL2 stop codon reduces e

57 e and found that LckCre-mediated deletion of hnRNP L results in a decreased thymic cellularity caused

58 small interfering RNA-mediated depletion of hnRNP L and NF90 significantly impaired viral replicatio

59 tiple RNA recognition motif (RRM) domains of hnRNP L, synergizes with miR-297, reduces VEGFA mRNA tra

60 eracted with this ESS, and downregulation of hnRNP L expression induced an increase in the caspase-9a

61 n a mouse xenograft model, downregulation of hnRNP L in NSCLC cells induced a complete loss of tumori

62 g of hnRNP A1 and U1 snRNA and the effect of hnRNP L on splicing.

63 Although expression of hnRNP L lowered the caspase-9a/9b ratio in NSCLC cells,

64 se-9a/9b ratio in NSCLC cells, expression of hnRNP L produced the opposite effect in non-transformed

65 2 to compensate for the weakened function of hnRNP L.

66 RNA immunoprecipitation of hnRNP L and hnRNP A1 revealed a binding motif located ce

67 Immunoprecipitation of hnRNP L followed by reverse transcription-polymerase cha

68 f hnRNP L, we validate numerous instances of hnRNP L-dependent alternative splicing of genes critical

69 ing T cell differentiation, and knockdown of hnRNP L or hnRNP A1 results in the lower induction of Tr

70 Finally, higher levels of hnRNP L protein associate with lower burden of UNC13A cr

71 ing splice site strength on the mechanism of hnRNP L function.

72 re identifies a cancer-specific mechanism of hnRNP L phosphorylation and subsequent lowering of the c

73 on-induced posttranslational modification of hnRNP L correlates with a modest increase in the protein

74 ed by the AKT pathway via phosphorylation of hnRNP L.

75 Importantly, based on the binding profile of hnRNP L, we validate numerous instances of hnRNP L-depen

76 Removal of hnRNP L by immunoprecipitation specifically abolished fo

77 To investigate the role of hnRNP L further, we have generated conditional hnRNP L k

78 A wider role of hnRNP L in mRNA translation was suggested by the decreas

79 ells, in agreement with the critical role of hnRNP L throughout T cell biology.

80 tion studies defined the RNA-binding site of hnRNP L as a 21-base-long sequence, 5'-CACCCACCCACAUACAU

81 IP-seq) to identify the RNA binding sites of hnRNP L within the transcriptomes of human CD4(+) and cu

82 Functionally, SETD2 regulates a subset of hnRNP L-targeted AS events.

83 However, the spectrum of direct targets of hnRNP L activity in T cells has yet to be defined.

84 criptome-wide analysis of the RNA targets of hnRNP L in lymphoid cells and add to the functional unde

85 s and add to the functional understanding of hnRNP L in human biology.

86 Moreover, depletion of hnRNP-L, either in vitro or in vivo, leads to increased

87 air enzyme, and identify a novel function of hnRNP-L in transcriptional regulation.

88 polysomes, where a similar modest effect on hnRNP L (a GLUT-1 and VEGF 3'-untranslated region-bindin

89 This 2xTK49 PPE bound only hnRNP L.

90 Also, phospho-hnRNP L recruits DRBP76 (double-stranded RNA binding pro

91 Phosphorylated hnRNP L interfered with hnRNP U binding to C9/E3, and ou

92 The phosphorylated hnRNP L, in turn, promotes expression of the antiapoptot

93 lasmic accumulation of Tyr359-phosphorylated hnRNP L sequesters miR-574-3p, overcoming its decoy acti

94 demonstrating that the RNA-binding protein, hnRNP L, protects a subset of RNAs from degradation by N

95 One such hnRNP protein, hnRNP L, regulates alternative splicing (AS) by binding

96 two, primarily nuclear RNA-binding proteins, hnRNP L and NF90, with previously unrecognized proviral

97 The binding of one of these proteins, hnRNP-L, is significantly decreased by mutations that di

98 Recombinant hnRNP-L functions to repress exon inclusion in vitro in

99 d by its 3'UTR length and ability to recruit hnRNP L.

100 obal protein synthesis in cells with reduced hnRNP L levels.

101 the binding site for the splicing repressor, hnRNP L.

102 ng of PTB to the Cat-1 mRNA in vivo required hnRNP L.

103 n via interaction with the ribonucleoprotein hnRNP L-like (hnRNP LL) has prompted a more detailed stu

104 antly, the similarity that the mode of SETD2-hnRNP L interaction shares with other related protein-pr

105 omal degradation, whereas hypoxia stimulates hnRNP L phosphorylation at Tyr(359), inducing binding to

106 Thus, we conclude that hnRNP L plays roles in enhancing stability, polyadenylat

107 Here, we demonstrate that hnRNP L represses CD45 exon 4 by recruiting hnRNP A1 to

108 We find that hnRNP L binds preferentially to transcripts encoding pro

109 Our results indicate that hnRNP L regulates T cell differentiation and migration b

110 iption-polymerase chain reaction showed that hnRNP L specifically interacts with VEGF mRNA in hypoxic

111 Together, these studies demonstrate that hnRNP-L is the primary protein through which CD45 exon 4

112 th antisense oligodeoxyribonucleotide to the hnRNP L RNA-binding site, the VEGF mRNA half-life was si

113 er, it is unclear what factors contribute to hnRNP L-regulated AS events.

114 Together, hnRNP L and A1 induce extended contacts between the 5' s

115 A model in which hnRNP L stabilizes snRNP binding can explain both effect

116 ese findings show that hnRNP U competes with hnRNP L for binding to C9/E3 to enhance the inclusion of

117 ansferase SETD2, specifically interacts with hnRNP L in vitro and in vivo.

118 fied several key factors that co-purify with hnRNP L.

119 tingly, the proteins that bind together with hnRNP L differ for different exons that contain the ARS

120 in vivo is abolished by prior treatment with hnRNP L-specific siRNA.